Reproductive Medicine doi: 10.3390/reprodmed7020026

Authors: Dejan Mitić Sonja Pop-Trajković Marin Bašić Aleksandra Petrić Jelena Milošević Stevanović Predrag Vukomanović Mihailo Stanojević

Background: Data on assisted reproductive technology (ART) outcomes among Roma women are virtually absent from the literature, despite Roma being the largest and most socioeconomically marginalized ethnic minority in Europe. This study provides the first structured evaluation of IVF/ICSI outcomes among Roma women at a tertiary fertility center. Methods: A retrospective observational cohort study was conducted at the Clinic for Gynecology and Obstetrics, University Clinical Center Niš, Serbia (May 2010–September 2015). Roma (n = 88) and non-Roma women (n = 1197) undergoing IVF/ICSI were compared on baseline clinical, hormonal, and embryological parameters. Primary and secondary outcomes were clinical pregnancy and live birth, respectively. Multivariable logistic regression, propensity score matching (1:4, by age and AMH), first-cycle sensitivity analysis, and a machine learning pipeline (logistic regression, random forest, XGBoost) with SHAP interpretability analysis were applied. Results: Roma women were significantly younger (31.9 ± 4.0 vs. 34.5 ± 4.7 years; p < 0.001) and had a more favorable ovarian reserve profile (AMH 3.78 vs. 2.90 ng/mL; p = 0.004; FSH 6.87 vs. 8.23 IU/L; p < 0.001), yet had a markedly longer duration of infertility (9.3 vs. 6.3 years; p < 0.001). Clinical pregnancy rates (48.9% vs. 41.3%; p = 0.179) and live birth rates (28.4% vs. 30.9%; p = 0.720) were comparable between groups. In multivariable logistic regression and propensity score-matched analyses, Roma ethnicity was not an independent predictor of either outcome. XGBoost SHAP analysis ranked Roma ethnicity last (11th of 11) in feature importance for both clinical pregnancy (mean |SHAP| = 0.033) and live birth (mean |SHAP| = 0.009). The dominant predictors were the number of embryos transferred, AMH, and age. Only 88 Roma women accessed ART over the decade-long study period, indicating profound underutilization of fertility services. Conclusions: No independent association was detected between Roma ethnicity and IVF/ICSI outcomes within the statistical power afforded by the Roma subgroup (n = 88). An exploratory first-cycle live birth signal (adjusted OR = 0.478; 95% CI 0.249–0.920; p = 0.027), not replicated in primary or propensity-matched analyses, is interpreted as hypothesis-generating. The extreme underutilization of ART services among Roma women remains the most clinically salient observation and a priority for targeted public health intervention.

Reproductive Medicine doi: 10.3390/reprodmed7020025

Authors: Roxana Ana Maria Dinescu Alexandru Catalin Motofelea Paul-Manuel Luminosu Alin Stefan Constantin Ioan Sas

Background: Sexual health is a fundamental pillar of well-being during the perinatal period. However, many studies suffer from scoring bias associated with zero values by failing to distinguish between women who are sexually inactive and those with physiological dysfunction. This study aimed to identify the distinct sociodemographic and psychological determinants of sexual inactivity versus sexual dysfunction quality in a Romanian perinatal cohort. Methods: An observational, cross-sectional study was conducted with 100 women (52% sexually active, 48% inactive). Participants were evaluated using the Female Sexual Function Index (FSFI), Patient Health Questionnaire-9 (PHQ-9), RSES (Rosenberg Self-Esteem Scale), and Generalized Anxiety Disorder-7 (GAD-7). Data were analyzed using binary logistic regression for activity status and multiple linear regression for functional quality. Results: Among sexually active women, 84.6% met the clinical criteria for sexual dysfunction (median FSFI = 21.6). Binary logistic regression revealed that self-esteem (RSES) was the sole independent predictor of sexual activity status (aOR = 1.144; 95% CI: 1.028–1.217, p = 0.016). Conversely, multiple linear regression showed that depression (PHQ-9) was the only significant independent predictor of functional quality (B = −0.73, p = 0.006). Maternal age, residence, and obstetric history did not significantly predict either outcome. Conclusions: Based on the findings of our preliminary, exploratory study, we propose a conceptual interpretation, framing perinatal sexuality as a potential two-stage process, where self-esteem appears to serve as a primary behavioral barrier for the resumption of intimacy, while depression serves as the primary disruptor of functional quality. Clinical interventions may benefit from moving beyond physical recovery to include psychological screening for body image and mood disorders to restore sexual quality of life.

Reproductive Medicine doi: 10.3390/reprodmed7020024

Authors: Francesca K. Martino Lucia F. Stefanelli Marianna Alessi Alessandra Zambon Monica Vedovato Maria Cristina Crepaldi Giovanni Samassa Leda Cattarin Dorella Del Prete Federico Nalesso

Background: Pregnancy following liver and kidney transplantation is rare. The presence of a rare genetic disorder and advanced chronic kidney disease (CKD) further complicates clinical management, for which evidence-based guidelines are limited. Case presentation: A 29-year-old woman with Alagille syndrome underwent combined liver and kidney transplantation in early childhood. She had stage 4 CKD, and her baseline creatinine was around 250 umol/L. Her pregnancy was unplanned and diagnosed at 19+1 weeks of gestation. After the diagnosis of pregnancy, immunosuppressive therapy was promptly adjusted, and potentially teratogenic medications were discontinued. At 21+1 weeks’ gestation, creatinine and urea levels rose despite multidisciplinary management, and she started renal replacement therapy. Despite ongoing multidisciplinary care, the pregnancy was complicated by placental abruption at 24+5 weeks, requiring a preterm cesarean section. A live-born female infant weighing 590 g was delivered. Discussion: The coexistence of CKD, long-term immunosuppression, and high obstetric risk requires early multidisciplinary assessment and individualized management. Currently, standardized protocols for monitoring and treatment are lacking in this rare population, making clinical decision-making particularly challenging, especially regarding CKD progression. Conclusion: Pregnancy in women with combined liver and kidney transplantation and advanced CKD carries a high risk of severe renal and obstetric complications. Preconception counseling and early referral to multidisciplinary teams may help improve management in similar rare clinical scenarios.

Reproductive Medicine doi: 10.3390/reprodmed7020023

Authors: El Oulidi Mounia Naoual Azzouzi Mouna Habbane Hind Hassani Idrissi Mounir Filali Sara El Janahi Francis Galibert Omar Akhouayri

Male infertility, implicated in nearly 50% of couples’ infertility cases, represents a major medical and sociocultural challenge in Morocco. This narrative review synthesizes available epidemiological, etiological, and genetic data within national and international contexts. In Morocco, male infertility is characterized by the frequent involvement of modifiable factors, notably varicocele, smoking, and occupational exposures. From a genetic standpoint, chromosomal abnormalities, particularly Klinefelter syndrome, together with Y chromosome microdeletions, especially within the AZFc region, represent the main identified etiologies. Emerging technologies, such as next-generation sequencing, offer promising diagnostic perspectives, although their clinical application remains limited and mainly confined to research. Despite advances in medically assisted reproduction, the management of male infertility in Morocco continues to face psychosocial and economic barriers, as well as inequalities in access to care. These findings underscore the need to establish national registries, conduct multicenter studies, and facilitate the translation of innovations (particularly multi-omics approaches) into clinical practice to improve male infertility management in the Moroccan context.

Reproductive Medicine doi: 10.3390/reprodmed7020022

Authors: Christina Pappa Muhammad Fatum Haya Nasser Umniah Khajori Danielle Christmas Nouf Khalifeh Mohammad Daas Moiad Alazzam

As survival rates among patients with gynaecological cancers continue to improve, fertility preservation has become an increasingly important aspect of comprehensive cancer care, particularly for younger women diagnosed during their reproductive years. The impact of treatment on fertility varies according to cancer type, stage, and modality, necessitating individualised preservation strategies. Fertility preservation is both feasible and safe in carefully selected patients with early-stage gynaecological cancers. Oocyte and embryo cryopreservation remain the most widely accepted techniques, particularly when time allows for ovarian stimulation. Fertility-sparing surgeries, such as radical trachelectomy and conservative management of early endometrial cancer, have shown promising oncological and reproductive outcomes. However, barriers including access, timing, and awareness continue to limit broader implementation. In modern society, fertility-preserving strategies should form an integral part of treatment planning for reproductive-aged women with gynaecological malignancies. Early referral to a fertility specialist, patient-centred counselling, and a coordinated multidisciplinary approach are essential to optimise both oncological and reproductive outcomes. Further research and education are required to refine guidelines and expand access to fertility-preserving care. This review presents the current fertility preservation options available to women with gynaecological cancers, including cervical, ovarian, and endometrial malignancies, and highlights the importance of early multidisciplinary intervention in delivering personalised care.

Reproductive Medicine doi: 10.3390/reprodmed7020021

Authors: Bridie Mulholland Isabella Conomos Alice Harper Lucy Pollock Sarah Sowry Pierre Hofstee

Background: Bushfire smoke exposure (BFSE) is associated with adverse pregnancy and neonatal outcomes; however, the specific impact of BFSE on pregnancies complicated by asthma is not well characterised. Methods: A retrospective cohort study analysed data from 22,166 pregnant women who gave birth in the Illawarra Shoalhaven region between January 2017 and December 2022. Women with asthma were identified by the ICD-10-AM code for asthma during hospital admission for birth. Exposure was defined using a fixed time-window assumption. Women were considered exposed to bushfire smoke if they experienced at least 4 weeks of their pregnancy between 25 October 2019 and 4 February 2020. Results: Prevalence of asthma in the total population was 8.31%. In the control cohort, outcomes for pregnant women with asthma were poorer than those without. Pregnant women with BFSE had increased odds of postpartum haemorrhage (OR 1.603; 95% CI 1.42–1.81), and decreased odds of gestational hypertension (OR 0.615; 95% CI 0.49–0.77), gestational diabetes mellitus (OR 0.703; 95% CI 0.63–0.79) and preterm birth (OR 0.813; 95% CI 0.67–0.98). Maternal asthma did not confound the relationship between BFSE and any of the primary study outcomes. Conclusions: This study emphasises the independent effects of asthma on pregnancy outcomes. The impact of BFSE on pregnant women with asthma remains unclear. Further research is needed to characterise the true effect of BFSE on pregnancies, uncomplicated and complicated by asthma.

Reproductive Medicine doi: 10.3390/reprodmed7020020

Authors: Erdenesuvd Damdinsuren Purevjargal Naidansuren Bum Chae Choi Duuriimaa Otgonbayar Temuujin Yuruult Mendsaikhan Gochoo Bolorchimeg Baldandorj

Background: In recent years, time-lapse incubators (TLs), which can maintain a stable culture environment, have been developed for use in in vitro fertilization (IVF) treatment. Methods: In this retrospective cross-sectional study, data from 1200 women who visited the Creation and Love fertility center between April 2021 and October 2023 were reviewed. Among them, the electronic medical records of 400 women aged 22–45 years who underwent IVF treatment were selected and divided into two groups according to the type of incubator used: 100 in the TL group and 300 in the conventional incubator (CI) group, to evaluate differences in embryo development. Among these participants, pregnancy outcomes were assessed in 150 women who underwent day 3 (cleavage-stage) fresh embryo transfer. Controlled ovarian stimulation was performed using a standard antagonist protocol. The primary outcome was a good embryo rate, and the secondary outcomes were the clinical pregnancy rate and live birth rate. Results: The mean age of the study population was 34.6 ± 5.4 years. The groups had similar good embryo rates (67.7% vs. 65.5%, p = 0.84), clinical pregnancy rates (49.0% vs. 52.0%, p = 0.86), and live birth rates (35.0% vs. 42.0%, p = 0.76). Furthermore, subgroup analyses showed that the live birth rate in women aged ≥ 35 years was higher in the TL group than the CI group (38.0% vs. 23.4%, p = 0.03). Conclusions: Based on the comparative analysis of live birth rates between women cultured using TLs and those using the CI during day 3 fresh-embryo transfer cycles, our study demonstrated a statistically significant increase in live birth rates among women ≥ 35 years in the TL group.

Reproductive Medicine doi: 10.3390/reprodmed7020019

Authors: Judy Bittar Mattias Akouri Jynfiaf Francis Panagiotis Tsiartas Randa Akouri

Introduction: Ovarian tissue cryopreservation (OTC) has emerged as an important fertility preservation option for women and girls at risk of treatment-induced ovarian failure. However, long-term data on clinical utilization and reproductive outcomes remain limited. This study provides a 30-year regional overview of OTC practice in Western Sweden. Material and Methods: This retrospective observational cohort study included 60 patients who underwent OTC between 1995 and 2025 within a publicly funded regional fertility preservation program. Data on patient characteristics, indications, surgical approach, cryopreservation techniques, and reproductive outcomes were collected from medical records, tissue bank data, and fertility preservation registries. Results: Malignant diagnoses accounted for 51 cases (85%) of indications, most commonly hematologic malignancies and breast cancer, while 9 patients (15%) had benign conditions requiring gonadotoxic therapy. During follow-up, only one patient (1.7%) underwent ovarian tissue transplantation (OTT), resulting in recovery of endocrine function and a spontaneous twin pregnancy. Overall, 15 women (25%) achieved at least one pregnancy. Of these, 8 (13.3%) occurred spontaneously without prior transplantation, 4 (6.7%) were achieved through oocyte donation, 1 (1.7%) occurred after OTT, and 1 patient (1.7%) had both spontaneous and donor-egg pregnancies. Most women (45/60, 75%) had no documented pregnancy or fertility treatment during follow-up. Conclusions: Over three decades, OTC has been successfully implemented as part of a regional fertility preservation program. However, the low rate of tissue utilization and the predominance of spontaneous pregnancies highlight the gap between tissue preservation and clinical use. These findings underscore the need for improved patient selection, structured long-term follow-up, and individualized risk assessment to optimize the clinical impact of OTC.

Reproductive Medicine doi: 10.3390/reprodmed7020018

Authors: Radomir Anicic Milina Tancic-Gajic Jovana Kocic Dragutin Sretenovic Aleksandar Dmitrovic

Background: Infertility is a growing global public health concern associated with reduced quality of life and increased anxiety and depressive symptoms across diverse populations. However, factors influencing mental health in women undergoing infertility treatment remain insufficiently understood. This study aimed to assess psychological distress and identify factors associated with anxiety and depression in women receiving infertility treatment. Methods: A cross-sectional study was conducted at a leading regional infertility referral center. Women with confirmed infertility were consecutively recruited during routine visits. Psychological distress was assessed using the validated Patient Health Questionnaire-4. Demographic, reproductive, and clinical data were collected from self-report and medical records. Associations of infertility duration and age with comorbidities and other demographic variables were evaluated using appropriate parametric and nonparametric tests, and correlations were examined using Spearman’s rank coefficient. Results: The mean age was 34.9 ± 5.9 years and the median duration of infertility was 3 years. Nearly half of participants had mild psychological distress (49.3%), while 16.7% and 2.7% had moderate and severe distress, respectively; 32% screened positive for anxiety and 17.3% for depression. Longer infertility duration was significantly associated with higher depressive symptom scores, whereas other demographic and clinical variables showed no significant associations. Conclusions: Psychological distress is highly prevalent among women with infertility, with depressive symptoms increasing with longer infertility duration. These findings highlight the need for routine psychological screening and integration of mental health support into infertility care in clinical practice and long-term treatment planning, emphasizing a comprehensive, patient-centered approach to reproductive medicine.

Reproductive Medicine doi: 10.3390/reprodmed7020017

Authors: Huy Phuong Tran Long Nu-Hai Nguyen Vy Nguyen-Thao Do Ngoc Thanh Truong Chau Kim Mai Tuyet Thi-Diem Hoang Ha Le-Bao Tran Trang Nguyen-Khanh Huynh

Background/Objectives: Hyaluronic acid (HA) has been proposed as a physiological alternative to polyvinylpyrrolidone (PVP) for sperm immobilization during intracytoplasmic sperm injection (ICSI). This prospective sibling-oocyte study aimed to compare embryological outcomes and morphokinetic parameters between HA and PVP. Methods: A total of 811 sibling-oocytes from 51 ICSI cycles were allocated to the HA group (SpermCatch; n = 377) or the PVP group (10% PVP Solution; n = 434). Fertilization outcomes, cleavage, blastocyst formation, and good-quality embryo development were assessed. Embryo morphokinetic parameters (t2–tB) and an AI-derived embryo score were analyzed in a subset of blastocysts with available time-lapse data. Results: The fertilization rates were comparable between the HA and PVP groups (80.9% vs. 85.3%, p = 0.25), as were the cleavage rates (99.0% vs. 97.0%, p = 0.27). However, the HA group had significantly lower rates of good-quality cleavage-stage embryos (33.4% vs. 47.9%, p < 0.01), blastocyst formation (52.3% vs. 69.9%, p < 0.01), and good-quality blastocysts (49.4% vs. 64.1%, p < 0.01). Morphokinetic timings did not differ significantly, whereas embryos in the HA group showed lower AI scores than those in the PVP group (p = 0.04). Conclusions: In this prospective sibling-oocyte cohort, HA-based sperm immobilization did not improve embryological outcomes compared with conventional PVP-assisted ICSI. Differences observed at the blastocyst stage should be interpreted cautiously and require confirmation in larger, randomized studies with clinical follow-up.

Reproductive Medicine doi: 10.3390/reprodmed7010016

Authors: Mark I. Evans Lawrence D. Devoe Gregory F. Ryan David W. Britt Christian R. Macedonia

Background/Objectives: Women’s health has historically lagged behind other medical specialties in transformative innovation, despite significant technological advances in adjacent fields. In this collection of papers, we examine the current state of innovation in women’s health and maternal–fetal medicine, identify barriers to transformation, and propose strategies for accelerating breakthrough developments. This paper presents an overview of multiple forces and their often-competing relationships that influence the environment in which advances in multiple areas of healthcare have had to navigate to enter mainstream practice. An understanding of these forces is essential to explain why some new technologies are readily deployed into clinical practice while others take many years to be adopted. Understanding the entire “echo-system” around any specific technology provides a much fuller understanding of how any individual advance can make its way into actual utilization. Methods: We synthesized current literature on innovation in women’s health, analyzing technological advances in artificial intelligence, precision medicine, non-invasive diagnostics, and surgical robotics. We examined patterns of innovation adoption and barriers to implementation across multiple domains. Results: Several key areas presented in this paper and the following show promise for transformative change: artificial intelligence (AI)-driven diagnostics achieving expert-level performance in prenatal screening, precision medicine approaches transforming genetic disease management, and non-invasive monitoring technologies revolutionizing maternal–fetal care. However, systemic barriers including regulatory complexity, liability concerns, and institutional inertia continue to limit widespread adoption of numerous breakthrough technologies. Conclusions: The convergence of multiple technological advances, particularly artificial intelligence and precision medicine, positions women’s health for unprecedented transformation. Success requires fostering innovation-ready environments, embracing systems-awareness approaches, and maintaining focus on human-centered care while leveraging technological capabilities with continual feedback and course corrections.

Reproductive Medicine doi: 10.3390/reprodmed7010015

Authors: Ioanna Bogiatzi Giannoula Kyrkou Kleanthi Gourounti Anastasia Bothou Eleni Tsoukala Panagiota Dourou Nikolaos Petrogiannis Vaidas Jotautis Antigoni Sarantaki

Background: Oocyte cryopreservation has emerged as a viable fertility preservation method, gaining popularity among women delaying motherhood for non-medical reasons. This study examines the awareness, perceptions, and social factors influencing young women’s decisions regarding elective oocyte cryopreservation (EOC), intending to identify key demographic and psychosocial determinants. Methods: A cross-sectional study was conducted using an online survey distributed via digital platforms between November 2024 and February 2025. A structured questionnaire comprising 31 multiple-choice questions assessed participants’ sociodemographic characteristics, reproductive health history, lifestyle factors, and perceptions of fertility and EOC. Statistical analyses included Chi-square tests, t-tests, and binary logistic regression to identify factors associated with willingness to undergo EOC. Results: A total of 390 women (mean age 22.57 ± 1.41 years) participated. Awareness of oocyte cryopreservation was remarkably high (93.1%). Significant predictors for the intention to undergo EOC included higher educational attainment (Master’s level) (OR = 4.27, 95% CI: 1.10–16.48) and living in a student dormitory (OR = 15.39, 95% CI: 4.86–48.71). Conversely, living with a partner showed a non-significant downward trend in interest (OR = 0.07, 95% CI: 0.01–1.43). Psychological factors, specifically anxiety about future fertility (OR = 0.23, 95% CI: 0.08–0.62 for moderate vs. high anxiety) and a strong desire for future parenthood (OR = 21.75, 95% CI: 1.45–32.99), also emerged as primary drivers of women’s reproductive decisions. Conclusions: Despite high awareness, the willingness to undergo elective oocyte cryopreservation remains limited. Targeted fertility education and supportive policies are needed to address misconceptions, financial barriers, and psychological concerns influencing reproductive decision-making. Further research should explore longitudinal trends in women’s attitudes toward EOC.

Reproductive Medicine doi: 10.3390/reprodmed7010014

Authors: Suhaib Khayat

Pregnancy (HP), defined as the coexistence of intrauterine and ectopic gestations, is a rare condition, especially in spontaneous conception, but it is a life-threatening obstetric emergency when rupture occurs, with a reported maternal mortality rate of 0.03%. Diagnosis is often delayed because confirmation of an intrauterine pregnancy can mask clinical signs of a concurrent ectopic gestation. Early recognition and prompt surgical intervention are therefore critical to maternal safety and preservation of intrauterine viability. This case highlights the diagnostic challenges and successful management of a spontaneous ruptured heterotopic pregnancy. Case presentation: A 34-year-old Middle Eastern woman, gravida 4, with a spontaneous conception, presented with sudden severe lower abdominal pain and signs of acute hemoperitoneum (hypotension, tachycardia, and marked peritoneal signs). Transvaginal ultrasound demonstrated a viable intrauterine pregnancy at 9 weeks 4 days gestation, together with a ruptured left tubal ectopic pregnancy of similar gestational age. The patient underwent urgent laparoscopic left salpingectomy with evacuation of approximately 1200 mL of intraperitoneal blood and clots. Postoperatively, she developed significant anemia (hemoglobin drop from 11.2 g/dL on admission to 6.5 g/dL) requiring transfusion of four units of packed red blood cells. Serial ultrasonographic follow-up confirmed ongoing viability of the intrauterine pregnancy, which ultimately resulted in a live birth at term. Progressive resolution of the postoperative pelvic hematoma was also noted. Conclusions: Ruptured heterotopic pregnancy remains a diagnostic and therapeutic challenge. This case, along with a synthesis of the contemporary literature, demonstrates that a high clinical index of suspicion, timely ultrasound diagnosis, and immediate minimally invasive surgical management are paramount. Furthermore, rigorous postoperative monitoring and resuscitation, including targeted transfusion, are essential to achieve maternal stabilization while allowing continuation of a viable intrauterine pregnancy, with reported live birth rates exceeding 70% following timely intervention.

Reproductive Medicine doi: 10.3390/reprodmed7010013

Authors: Ahmad Sahely Ramzi Abdu Alajam Fooz Waheed Aryam Areeshi Abeer Eissa Rahaf Alharbi Amira Kappi Basema Temehy

Background/Objectives: Primary dysmenorrhea is a common menstrual condition that significantly affects women’s daily functioning and quality of life. Although physiotherapy has been shown to reduce menstrual pain, the awareness of these methods in Saudi Arabia remains unclear. This study aimed to assess women’s awareness and experiences of physiotherapy methods for managing primary dysmenorrhea in Saudi Arabia. Methods: A cross-sectional online survey was conducted among women living in SA between 16 and 28 February 2024. The questionnaire collected information on six sections including on sociodemographic characteristics, menstrual history and pain severity, work-related impact, pain-management practices, healthcare utilisation, and awareness and use of physiotherapy modalities. Convenience sampling was employed, and participation was voluntary and anonymous. Descriptive data analysis was performed using SPSS software. Results: A total of 431 women participated; most were Saudis (91.9%) and aged 18–24 years (43.2%). Primary dysmenorrhea was reported by 86.5% of participants. More than half (58%) had used at least one physiotherapy-related method, mainly heat, massage, or exercise, and 55.2% considered these methods effective. However, most relied on basic home strategies rather than structured physiotherapy interventions. Additionally, 60.8% expressed willingness to use physiotherapy in the future. Conclusions: Despite the frequent use of simple home-based methods, structured physiotherapy interventions remain underutilised. Increasing public education, improving access to physiotherapy services, and integrating self-management guidance and telerehabilitation into women’s health programmes may enhance menstrual pain management and overall quality of life.

Reproductive Medicine doi: 10.3390/reprodmed7010012

Authors: Ramilya K. Potapova Madina E. Ospanova Saniya A. Abdrakhmanova Aizhan T. Makisheva Nikolay A. Popkov Kuralai H. Zhangaziyeva Balzhan S. Bekmakhanova

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Reproductive Medicine doi: 10.3390/reprodmed7010011

Authors: Christos Anthoulakis Eirini Iordanidou Theodoros Theodoridis Grigoris Grimbizis

Background/Objectives: Dichorionic triamniotic (DCTA) triplet pregnancies are associated with increased rates of placenta-specific complications primarily attributed to vascular anastomoses in the monochorionic (MC) pair. Selective fetal reduction to twins (of one of the MC pair) is a complex and not a widely available procedure. Multifetal reduction (MFR) to singleton pregnancy can reduce adverse pregnancy outcomes but is controversial due to medico-legal and socio-ethical issues. The aim of this study is to identify the rate of miscarriage < 24 weeks or preterm birth < 34 weeks following MFR to singleton pregnancy in DCTA triplets and compare the results with expectant management. Methods: This systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the Prospective Register of Systematic Reviews System (ID: CRD42023422585). Results: Overall, from 21 citations of relevance, 6 studies with a total of 548 DCTA triplet pregnancies fulfilled the inclusion/exclusion criteria. In comparison with expectant management (n = 336), meta-analysis demonstrated that MFR to singleton pregnancy (n = 212) was associated with a lower rate (9.4% vs. 48.5%) of preterm birth (RR = 0.19, 95%CI 0.07–0.51), whereas the rate of miscarriage (14.6% vs. 9.2%) did not significantly increase (RR = 1.53, 95%CI 0.91–2.55). Conclusions: In DCTA triplet pregnancies, MFR to singleton pregnancy was associated with a reduced preterm birth rate and not associated with an increased miscarriage rate. Given the fact that the MC pair is reduced only to lower the rate of preterm birth, appropriate counselling and justification are important. In the absence of randomized controlled trials, data from systematic reviews are the best available evidence for counseling on the different management options.

Reproductive Medicine doi: 10.3390/reprodmed7010010

Authors: Hilary Zhang Abbey Kalay Jeffrey Pea Faith E. Carter Effat Rahman Brittany Y. Jarrett Kathleen M. Hoeger Sujata Kar Marla E. Lujan

Background/Objectives: Geographical differences exist in the clinical presentation of polycystic ovary syndrome (PCOS). The degree to which ovarian morphology contributes to this variability is unknown. Methods: This study compared ovarian ultrasound features between women with PCOS residing in two geographical regions (India and the United States) using stored de-identified ultrasound scans from 331 women with PCOS. Sonographic markers of interest included follicle number per ovary (FNPO), follicle number per cross-section (FNPS), ovarian volume (OV), ovarian area (OA), stromal area (SA), and stromal-to-ovarian area ratio (S/A). Results: Most participants in both regions met the accepted criteria for polycystic ovarian morphology (India 87% vs. U.S. 83%). The U.S.-based group had a higher prevalence of follicle excess (41% in U.S. vs. 29% in India; p = 0.037), whereas the prevalence of ovarian enlargement was similar across groups (India 37% vs. U.S. 31%, p = 0.252). FNPS was higher in the U.S.-based group (p = 0.046), while the India-based group had higher OV (p = 0.010). SA and S/A did not differ between groups, albeit OA was slightly larger in women with PCOS from India (p = 0.022). Associations between ovarian morphology and menstrual cycle length (ρ = 0.16–0.25), hirsutism score (ρ = 0.19–0.23), and total testosterone (ρ = −0.33–0.42) were noted in both groups (p < 0.05). Conclusions: Some variation in ovarian morphology may exist across geographic regions. However, the degree of variability is unlikely to warrant regional definitions for polycystic ovarian morphology at this time.

Reproductive Medicine doi: 10.3390/reprodmed7010009

Authors: Manisha Chavan Sameena Tabassum Divya Dinesh Joshi Kusalik Boppana Nasreen Banu Riya Kayarkar Kalp Chauhan Gayathri Yerrapragada Poonguzhali Elangovan Mohammed Naveed Shariff Thangeswaran Natarajan Jayarajasekaran Janarthanan Shreshta Agarwal Sancia Mary Jerold Wilson Mini Virmani Atishya Ghosh Mimi Adu Serwaah Shiva Sankari Karuppiah Keerthy Gopalakrishnan Divyanshi Sood Swetha Rapolu Swathi Priya Cherukuri Shivaram P. Arunachalam

Background/Objectives: Precocious puberty (PP), defined as the onset of secondary sexual characteristics before 8 years in girls and 9 years in boys, is associated with psychosocial distress, compromised adult height, and long-term metabolic risk. Early identification remains challenging, as current diagnostic approaches are largely reactive and rely on invasive or resource-intensive testing. This narrative review examines how artificial intelligence (AI) can support earlier risk prediction and detection of PP through integration of clinical, hormonal, imaging, lifestyle, and environmental data. Methods: A narrative literature review was conducted using PubMed, Scopus, Embase, Web of Science, and Google Scholar to identify relevant studies published between 2005 and 2025. Eligible studies included original research and high-quality reviews that examined AI-based approaches, such as machine learning and deep learning, in pediatric endocrinology, particularly for the prediction or diagnosis of central or peripheral precocious puberty. Studies incorporating clinical, hormonal, radiological, lifestyle, environmental, or multi-omics data relevant to AI modeling were included. Results: AI models, including XGBoost, random forest, convolutional neural networks, and regression-based approaches, have demonstrated potential utility in predicting central precocious puberty using hormonal, imaging, and growth data. Reported applications include automated bone age assessment, lifestyle and dietary risk stratification, and exploratory use of wearable-derived behavioral data. However, progress is limited by small pediatric datasets, population bias, limited interpretability, and unresolved ethical challenges related to privacy, consent, and equity. Conclusions: Artificial intelligence represents a promising decision-support approach for earlier, non-invasive, and individualized risk assessment in precocious puberty. Future progress will depend on the integration of longitudinal, multimodal data, the development of ethical models, and interdisciplinary collaboration among pediatric endocrinologists, data scientists, and public health stakeholders.

Reproductive Medicine doi: 10.3390/reprodmed7010008

Authors: Raghda Youssef Caroline Aimone-Vianna Evelyne Schvoerer Alain Lozniewski Anne Julie Fattet

Background/Objectives: Infertility is a major public health concern, affecting one in six individuals worldwide and nearly one-quarter of couples in France. While a male, female, or combined factor can be identified in approximately 75% of cases, infertility remains unexplained in 10–25%. Genital tract infections account for roughly 15% of male infertility cases and are often asymptomatic, being detected incidentally during routine evaluation prior to assisted reproductive technology (ART). Emerging evidence suggests that the seminal microbiota may contribute to sperm quality and male reproductive health. This systematic review aims to evaluate whether specific microbial profiles are associated with alterations in semen parameters. Methods: A comprehensive literature search was conducted in PubMed and ScienceDirect, yielding 165 and 1418 records, respectively. In the end, 20 articles were included in this systematic review. Results: Men with normal semen parameters commonly exhibited a higher abundance of Lactobacillus and Bifidobacterium, whereas Prevotella was more frequently observed in individuals with impaired semen quality. Several taxa—such as Gardnerella, Corynebacterium, and Staphylococcus spp.—were detected in both normal and altered semen profiles, suggesting that their impact on sperm quality may depend on reaching a pathogenic threshold. Conclusions: Current evidence supports an association between seminal microbiota composition and sperm quality. However, the heterogeneity of available studies and the lack of standardized methodologies limit the ability to draw firm conclusions. Further well-designed studies are required to clarify causal relationships and to determine the clinical relevance of seminal microbiota assessment in male infertility.

Reproductive Medicine doi: 10.3390/reprodmed7010007

Authors: Tajamul Hussain

Background/Objectives: Dynein axonemal heavy chain (DNAH) genes, including DNAH6, are implicated in male infertility, particularly multiple morphological abnormalities of the spermatozoa flagellum (MMAF). However, an underlying mechanism is unclear. Methods: This in silico study analyzed 19 previously reported DNAH6 mutations to elucidate their effects on the structural, mechanical, and microstructural aspects and axonemal assembly of flagellum and how these changes impact reproductive health, correlating with pathogenicity scores, ATP binding capacity, and protein interactions. Results: DNAH mutations were associated with CDGP (52.63%), male infertility (36.84%), and primary ovarian insufficiency (10.53%). MMAF-linked mutations exhibited higher SNAP2 scores (57.25 ± 5.68 vs. −32.58 ± 44.85, p = 0.002), reduced ATP binding affinity (−6.27 ± 4.20 vs. −8.92 ± 0.23 kcal/mol, p = 0.05), and smaller catalytic cavity size (17,646 ± 13,005 vs. 27190 ± 3485 Å3, p = 0.04). These mutations showed reduced DNAH6-CLIP4 binding affinity (−303.90 ± 5.23 vs. −313.60 ± 4.28 kcal/mol, p = 0.002). Literature-based semen analysis revealed correlations between Phred scores and absent flagella (r = 0.952, p = 0.012) and inverse correlations between ATP binding capacity and absent flagella (r = −0.902, p = 0.036) or irregular width (r = −0.949, p = 0.014). A mathematical model of ATP binding kinetics predicted reduced flagellar motility in MMAF mutants due to impaired dynein function. Ultrastructural analyses indicated that high pathogenicity scores and reduced ATP binding correlate with absent inner dynein arms and radial spokes, while impaired DNAH6-CLIP4 interactions disrupt axonemal assembly. Conclusions: In silico analyses, integrated with microstructural, axonemal, and mathematical modeling data, demonstrate that DNAH6 mutations cause MMAF by impairing ATP binding, protein interactions, and axonemal assembly, leading to severe flagellar dysfunction and thereby negatively affecting reproductive health.

Reproductive Medicine doi: 10.3390/reprodmed7010006

Authors: Tatyana Breizman Shahar Kol

Background: Following gonadotropin-releasing hormone (GnRH) agonist trigger and “freeze all” in order to prevent ovarian hyper-stimulation syndrome (OHSS), patients are usually anxious to continue immediately with a frozen embryo transfer (FET). Currently, the preferred FET protocol in based on natural or induced ovulation. Objectives: Do ovarian stimulation and GnRH-a, used to trigger final oocyte maturation, affect the reproductive axis in the next natural cycle? Design: An observational case series of 100 subsequent in vitro fertilization (IVF) patients to whom GnRH-a (Triptorelin 0.2 mg) was given for final oocyte maturation in the context of ovarian hyper-stimulation syndrome prevention, followed by embryos “freeze all”. Methods: In the next natural cycle, patients were followed to detect a dominant follicle (≥17 mm), at which time ovulation was triggered with human chorionic gonadotropin (hCG, 250 µg), and FET was scheduled according to embryo’s age on freezing day. Results: Whereas natural ovulation according to pre-IVF treatment was predicted to be on cycle day 14, the actual hCG-scheduled ovulation in our patients was on day 21. In eight patients, follicular activity was not detected after 15–28 days; therefore, the natural cycle frozen embryo transfer approach was abandoned. Conclusions: Ovarian stimulation and GnRH-a used to trigger final oocyte maturation in IVF patients inhibits the reproductive axis for days. Therefore, natural ovulation in the subsequent cycle may be deferred for about one week relative to the patient’s pre-IVF menstrual cycle pattern. This may help schedule clinic visits to optimize monitoring efficiency.

Reproductive Medicine doi: 10.3390/reprodmed7010005

Authors: Tilman Born Liv Gesslein Georgia Cole Maurice Kappelmeyer Angela Köninger Maximilian Rauh

Background/Objectives: Preterm birth remains a major cause of neonatal morbidity and mortality, particularly in multiple pregnancies and in cases of cervical shortening. While cervical cerclage is established in singleton pregnancies, its efficacy in multiple gestations remains uncertain. This study compares pregnancy and neonatal outcomes following second-trimester cerclage in singleton and multiple pregnancies with a short cervix. Methods: In this retrospective cohort study, 96 women underwent second-trimester cerclage at a tertiary perinatal center between 2020 and 2024. All had a cervical length ≤ 25 mm or prolapsed membranes without infection or premature rupture. Primary outcomes included term delivery rate, gestational age, mode of delivery, and neonatal outcomes; secondary outcomes comprised surgical complications and rehospitalization, defined as the need for renewed inpatient care due to threatened preterm labor or procedure-related complications. Results: In total, 79 singleton and 17 multiple pregnancies were analyzed. Term delivery occurred more often in singletons (54%) than multiples (18%, p = 0.006). Mean gestational age at birth was 258 ± 25 days in singletons versus 228 ± 28 days in multiples (p < 0.001). Birth weight was significantly lower in multiples (1985 g vs. 2943 g; p < 0.001), and neonatal infections were more frequent (53% vs. 26%; p = 0.008). Caesarean delivery was more common in multiples (82% vs. 33%; p < 0.001). Apart from increased postoperative contractions in multiples (24% vs. 5%; p = 0.031), complication rates and rehospitalization (27% vs. 29%; p = 0.8) were similar. Conclusions: Second-trimester cerclage is less effective in preventing preterm birth in multiple pregnancies compared to singleton pregnancies; however, it appears to be associated with a stabilizing clinical course and may facilitate outpatient management in selected high-risk cases. These findings support individualized counseling and shared decision-making, particularly in multifetal gestations.

Reproductive Medicine doi: 10.3390/reprodmed7010004

Authors: Matteo Lazzeroni Mario Lentini Antonella Maruca Pasquale Capaccio Jerome Rene Lechien Basilio Pecorino Benito Chiofalo Giuseppe Scibilia Salvatore Maira Paolo Scollo Antonino Maniaci

Obstructive sleep apnea (OSA) is a highly prevalent disorder with far-reaching systemic consequences. While its cardiometabolic and neurocognitive impacts are well established, growing evidence highlights OSA as a contributor to infertility in both men and women. The pathophysiological mechanisms include intermittent hypoxia, oxidative stress, systemic inflammation, and endocrine disruption, all of which can impair spermatogenesis, reduce semen quality, alter gonadal hormone secretion, and compromise ovarian function. Clinical studies consistently demonstrate associations between OSA and impaired semen parameters, reduced testosterone, and erectile dysfunction in men. In women, OSA is frequently observed in those with polycystic ovary syndrome, is associated with ovulatory dysfunction, and negatively affects in vitro fertilization outcomes, pregnancy rates, and miscarriage risk. Despite these findings, infertility is not systematically included in global burden estimates of OSA, leading to the underestimation of its true health and socioeconomic impact. Therapeutic strategies such as weight loss, continuous positive airway pressure, and integrative approaches show promise, though robust evidence from randomized trials is still lacking. Integrating sleep health into reproductive medicine may provide a cost-effective and equitable pathway to improve fertility outcomes worldwide.

Reproductive Medicine doi: 10.3390/reprodmed7010003

Authors: Alessandro Messina Alessandro Libretti Daniele De Ruvo Paolo Alessi Giovanni Lipari Tiziana Bruno Daniela Caronia Sofia Vegro Livio Leo Bianca Masturzo

Background: Retained products of conception (RPOC) after term delivery are uncommon but may lead to persistent abnormal uterine bleeding and other complications. Hysteroscopic removal is considered the optimal management strategy, and technological advances have increasingly enabled operative procedures to be performed safely in an office setting. Clinical case: We report the case of a 43-year-old woman who presented with intermittent spotting four months after spontaneous vaginal delivery. Transvaginal ultrasound revealed a small, avascular hyperechoic intrauterine lesion consistent with retained amniochorionic tissue. She underwent office hysteroscopic removal using a 16 Fr bipolar mini-resectoscope under nitrous oxide (N2O) buccal–nasal analgesia. The procedure was performed using a vaginoscopic, no-touch approach without speculum, tenaculum, or cervical dilation. Complete resection was achieved in a seven-minute procedure, with a postoperative pain score of 2/10 on the VAS and no complications. At 30-day follow-up, the patient was asymptomatic, and an ultrasound confirmed complete resolution. Conclusion: This case demonstrates that retained amniochorionic tissue can be safely and effectively treated in a fully ambulatory setting using mini-resectoscopic technology and N2O analgesia. The combination of minimally invasive instruments, patient-centered procedural strategies, and well-tolerated analgesia supports the growing role of office operative hysteroscopy for selected complex intrauterine conditions.

Reproductive Medicine doi: 10.3390/reprodmed7010002

Authors: Israel Maldonado Rosas Filomena Mottola Ilaria Palmieri Lorenzo Ibello Jogen C. Kalita Shubhadeep Roychoudhury

The success of embryo implantation and pregnancy depends on a complex interaction between the trophoblast and the endometrial environment, where endometrial receptivity plays a crucial role in this process. Assisted reproductive technologies (ARTs) are essential in overcoming biological barriers and enabling implantation in women with fertility issues. However, one of the main challenges in ART is ensuring that the endometrium is receptive at the time of implantation. Therefore, identifying endometrial receptivity biomarkers is essential to optimize ART treatments, improving success rates. A comprehensive literature review was conducted by searching peer-reviewed articles published in PubMed, Scopus, and Web of Science databases. The search included studies focusing on molecular and cellular mechanisms underlying endometrial receptivity in both natural and stimulated cycles. Various experimental methods, including proteomic and microRNA studies, have identified key biomarkers involved in endometrial receptivity, such as adhesion molecules, growth factors, and others. However, ovarian stimulation in fertility treatments can alter endometrial receptivity, making approaches like frozen embryo transfer necessary. Despite advancements, many questions persist regarding the endometrial receptivity and implantation mechanisms in both natural and stimulated cycles. This article reviews the main molecules involved in endometrial receptivity in natural and stimulated cycles, highlighting their potential role as biomarkers for embryo implantation.

Reproductive Medicine doi: 10.3390/reprodmed7010001

Authors: Margarita Artemenko Yumiko Sakai Misaki Naito Katsuhiro Murakami Amane Harada Ayuko Kishimoto

Background/Objectives: Menstrual blood, a periodic uterine discharge, represents a non-invasive source for an indication of the functional status of the endometrium. While menstrual blood-derived stem cells have been extensively characterized and menstrual blood is considered a diagnostic material for the analysis of gynecologic pathology in research studies, it is not routinely used in clinical settings. To develop novel noninvasive diagnostic tools for endometrial status assessment, we aimed to characterize the morphological and molecular markers of menstrual blood. Methods: Menstrual blood samples were obtained from healthy volunteers and characterized macroscopically and microscopically using smears (May-Grunwald-Giemsa staining), confocal microscopy, and imaging flow cytometry (cluster of differentiation [CD]90, CD45, fibrin). Clot dissociation was performed to analyze the cellular composition of clots. Results: We morphologically characterized menstrual blood cells and identified three uterine-derived cells and cell cluster types (endometrial stromal, endometrial epithelial, and vaginal epithelial). Additionally, we confirmed the specificity of CD90 for endometrial stromal cell populations, which were separately characterized in the supernatant and menstrual blood clots using light and confocal microscopy, and we analyzed the composition of the menstrual blood supernatant and dissociated clots using imaging flow cytometry. Conclusions: The results of this study may serve as a foundation for the development of new non-invasive diagnostic tools for endometrial pathology for the potential support or replacement of highly invasive procedures, such as diagnostic dilation and curettage.

Reproductive Medicine doi: 10.3390/reprodmed6040044

Authors: Rishik Kapoor Manesh Kumar Panner Selvam Suresh C. Sikka

The recent trends in decreasing population all over the world are cause of concern, especially in developed countries. Socioeconomic factors as well as age, physiological, and environmental issues are the main contributors in limiting the number of children in modern families. In this regard, male reproductive health has recently attracted significant attention not only in the research community but also in our social platform. Key issues such as infertility and sexual dysfunction contribute to the decline in male reproduction. Socioeconomic status (SES) is the least understood factor that plays a critical role in influencing male reproductive health. The SES of an individual can be a key determinant of the type of infertility care they receive and may also predict fertility outcomes for couples undergoing assisted reproductive technology procedures. This mini review seeks to deepen our understanding of reproductive health equity by exploring the impact of socioeconomic and social factors on men’s sexual health and fertility outcomes. Our attempt is to reveal the complex interconnections between SES and male reproductive well-being.

Reproductive Medicine doi: 10.3390/reprodmed6040043

Authors: Usha Rani Balu Ramasamy Vasantharekha Hannah P. Priyanka Rahul S. Nair Gaurav Mudgal Seetharaman Barathi

Background: Preeclampsia (PE) and gestational diabetes mellitus (GDM) are complex pregnancy disorders characterized by hypertension, proteinuria, increased blood glucose levels, and metabolic dysfunction. Methods: We investigated lymphocyte proliferation, immune function, key antioxidants, and metabolic and mitochondrial enzyme activities in women with PE and PE with GDM compared to normotensive pregnant (NP) controls. Lymphocyte proliferation was assessed following phytohemagglutinin (PHA) stimulation at varying concentrations (0.5, 2.5, and 5 µg/mL). Activities of key antioxidant enzymes, metabolic enzymes, and mitochondrial enzymes were measured. Other stress markers, including nitric oxide (NO) production and lipid peroxidation (TBARS), along with acetylcholine esterase (AChE) activity, and proinflammatory cytokine assays (IL-6 and TNF-α) were also evaluated from the PHA-induced lymphocytes. Results: Lymphocyte proliferation in response to PHA was significantly increased in PE and PE with GDM groups compared to NP, although low-dose PHA (0.5 and 2.5 µg/mL) moderately enhanced proliferation in NP. IL-6 and TNF-α levels were notably elevated in both disease groups. Antioxidant activities of SOD, GST, GPx and AChE, Citrate synthase, Cytochrome c oxidase, and NO production were significantly reduced in PE and PE with GDM, while hexokinase activity involved in glycolysis was elevated in both groups. Further, TBARS levels were elevated in the disease groups, particularly in PE with GDM. Conclusions: The findings arise from a clinical cross-sectional study and highlight significant immune alterations, oxidative stress, and mitochondrial impairment in PE and PE with GDM. The observed elevation in proinflammatory cytokines further underscore the role of immune activation in the pathogenesis of these complications, emphasizing the integrated immunometabolic shifts identified in this study, as potential molecular indicators for early intervention.

Reproductive Medicine doi: 10.3390/reprodmed6040042

Authors: Ramilya K. Potapova Madina E. Ospanova Saniya A. Abdrakhmanova Aizhan T. Makisheva Nikolay A. Popkov Kuralai H. Zhangaziyeva Balzhan S. Bekmakhanova

Background/Objectives: Non-receptive endometrium is associated with recurrent implantation failure, which leads to a decrease in the frequency of pregnancy during IVF; therefore, new treatment methods such as the use of Platelet-Rich Plasma (PRP) are gaining popularity in the treatment of infertility in women with repeated unsuccessful IVF attempts. Methods: A total of 38 women were included in this study, with the main complaint being the inability to conceive or maintain pregnancy. Medical examination, laboratory tests, ultrasound of the pelvic organs and hysteroscopy were performed. After that, whole blood was taken to prepare an autologous PRP; then, the PRP was inserted into the uterine using an intrauterine catheter in the first phase of the menstrual cycle (1–7 procedures). The primary outcome of this study was an increase in endometrial thickness and improvement of the receptive endometrial layer. The secondary outcome was pregnancy rate. This was a single-center prospective interventional clinical study. Results: Statistical analysis of changes in endometrial thickness after PRP therapy showed that endometrial thickness indicators after treatment significantly exceeded the values before the intervention. This may be evidence of the effectiveness of PRP therapy for thin endometrium. When analyzing pregnancy status, it was noted that after receiving PRP, more than half (56% of cases) became pregnant and the majority of them successfully gave birth. Conclusions: Based on the results of our study, we can conclude that intrauterine injection of PRP may be a new therapeutic approach in the treatment of thin endometrium and associated infertility. The use of PRP demonstrated effectiveness in increasing the thickness of the endometrium, regardless of pregnancy, while the secondary indicator was the frequency of successful pregnancies among the participants.

Reproductive Medicine doi: 10.3390/reprodmed6040041

Authors: Yong-Jin Park Moon-Il Park

Background/Objectives: Cervical insufficiency remains a leading cause of second-trimester pregnancy loss and early preterm birth. Although single-level cerclage techniques such as McDonald or Shirodkar are widely accepted, the potential advantages of double or modified double-level cerclage remain controversial. Methods: This systematic review was conducted in accordance with PRISMA guidelines. Comprehensive searches of PubMed, Embase, Web of Science, and the Cochrane Library (to September 2025) were supplemented by Google Scholar and conference proceedings. Eligible studies included randomized controlled trials, comparative cohort studies, and case series directly comparing double versus single transvaginal cerclage. A total of twenty-six sources were included, spanning randomized trials, comparative cohort studies, published protocols, case series, systematic reviews, conference abstracts, and early technical or historical reports. The primary outcome was preterm birth before 34 weeks; secondary outcomes were GA at delivery, latency, neonatal morbidity and mortality, and maternal complications. Results: Across prophylactic (history- or ultrasound-indicated) settings, double sutures produced outcomes comparable to single-level cerclage without consistent superiority. In contrast, in emergency or exam-indicated cases with advanced cervical dilation or bulging membranes, double or double-level cerclage significantly prolonged latency and reduced very preterm birth (<32–34 weeks). Double-level reinforced techniques (including monofilament-based and modified Wurm-type approaches) showed improved mechanical support and lower neonatal intensive-care admission. Case series further demonstrated successful rescue procedures beyond 24 weeks, indicating expanded surgical feasibility in selected patients. Conclusions: While double cerclage yields similar results to single cerclage in prophylactic use, it appears advantageous in high-risk or emergency scenarios. Comparative analyses suggest that combined mechanical and infection-controlled approaches may improve cervical competence and prolong gestation in selected patients. Ongoing multicenter randomized trials are needed to establish its definitive role in modern obstetric practice.

Reproductive Medicine doi: 10.3390/reprodmed6040040

Authors: Bianca Brazzelli Alessandro Libretti Raphael Thomasset Massimiliano Natrella Alessandro Messina Livio Leo

Background: The management of symptomatic uterine fibroids in women of reproductive age remains a clinical challenge, with uterine preservation being a primary objective in order to safeguard fertility. To date, no clear consensus has been established in the literature regarding the optimal treatment strategy, as therapeutic choices largely depend on individual patient characteristics. In selected cases, the use of preoperative measures aimed at minimizing the risk of major intraoperative hemorrhage has been associated with an increased likelihood of adopting a more conservative surgical approach. Case presentation: We report the case of a young patient treated at our institution who presented large uterine fibroids and underwent Preoperative Uterine Artery Embolization (PUAE) before planned open myomectomy with positive outcomes. In our case, this approach provided excellent intraoperative hemostatic control, minimizing blood loss. At post-discharge follow-up, the patient showed marked symptom relief and improved quality of life. Long-term follow-up will assess sustained treatment efficacy. Conclusions: PUAE should be considered a valuable therapeutic option in patients with symptomatic uterine fibroids at high risk of surgical bleeding. When integrated into a multidisciplinary treatment plan, PUAE may enhance surgical safety, support fertility preservation, and broaden the range of conservative options available for women with complex fibroid disease.

Reproductive Medicine doi: 10.3390/reprodmed6040039

Authors: Cristiana Ribeiro Silva Ana Beatriz de Almeida Carolina Lemos Carla Leal Hélder Ferreira Márcia Barreiro

Background/Objectives: Serum progesterone (P) levels on the day of frozen–thawed embryo transfer (FET) appear to influence treatment success. Some studies suggest that low P levels may negatively affect pregnancy outcomes, whereas others report a detrimental impact of elevated p values. Although a threshold of 10 ng/mL is frequently cited as indicative of adequate luteal support, the optimal P cut-off on the FET day remains unclear. This study aims to identify a predictive serum p value above which pregnancy rates do not decline in artificial FET cycles. Methods: A retrospective cohort study comprising 236 women who underwent FET between November 2021 and July 2023 was conducted at the Center of Assisted Medical Procreation of Centro Materno-Infantil do Norte. Serum P levels were measured on the day of FET. Three analytical approaches were used in assessing the association between P levels and FET outcomes: (1) fixed threshold of 10 ng/mL; (2) stratification into quartiles (Q1 < 7.30; Q2: 7.30–10.26; Q3: 10.27–13.42; Q4 > 13.42 ng/mL); (3) optimal P cut-off derived from ROC analysis (9.34 ng/mL). Continuous variables were compared using T-test or One-Way ANOVA. Categorical variables were analyzed using Chi-square test or Fisher’s exact test. Associations between P levels and pregnancy outcomes were further examined using logistic regression. Results: Using the P threshold of 10 ng/mL, women with p < 10 ng/mL showed significantly lower positive β-hCG rates (p = 0.020), implantation rates (p = 0.002), and clinical pregnancy rates (CPRs) (p = 0.019). Quartile-based comparisons revealed no significant differences. Regarding the ROC-derived cut-off, women with p ≥ 9.34 ng/mL had significantly higher positive β-hCG rates (38.5% vs. 52.8%, p = 0.012), implantation rates (30.0% vs. 45.5%, p = 0.002), CPR (36.3% vs. 50.0%, p = 0.016), ongoing pregnancy rates (24.4% vs. 37.6%, p = 0.013), and live birth rates (24.4% vs. 37.6%, p = 0.013). p ≥ 9.34 ng/mL remained an independent predictor of improved pregnancy outcomes in multivariate analysis. Conclusions: Serum P levels ≥ 9.34 ng/mL on the day of FET were associated with significantly higher pregnancy success, supporting the relevance of center-specific P thresholds and suggesting potential benefit in individualized luteal phase support strategies.

Reproductive Medicine doi: 10.3390/reprodmed6040038

Authors: Marwan Habiba Ilary Ruscito Paola Bianchi Sun-Wei Guo Giuseppe Benagiano

We carried out a comprehensive literature search for publications on the range of vascular events that have been linked to adenomyosis. This covered vascular diseases, blood coagulation disorders, thrombosis, hypercoagulation, stroke (embolic, ischemic, thrombotic, hemorrhagic), cerebrovascular episodes, cerebral infarction, cerebral hemorrhage) and renal disease. This review covers 63 articles. Nineteen articles reported clinical manifestations of intravascular thrombosis in women with adenomyosis. Eleven publications were identified that reported on cerebral involvement and adenomyosis, including cases of ischemic stroke or infarction. Dysregulation primarily seems to occur via local factors leading to altered angiogenesis. Five case reports were identified that reported on various vascular complications attributed to the presence of adenomyosis. The search also identified reports of cerebral complications in women with adenomyosis. Through a secondary search, we identified publications dealing with a possible connection between cardiac complications and renal pathology, which the authors attributed to adenomyosis. Vascular involvement in adenomyosis is documented in rare cases by the presence of endometrial tissue in myometrial vessels both in menstrual and non-menstrual uteri. Women with adenomyosis have a higher platelet count, a shorter thrombin and prothrombin time and an activated partial thromboplastin time. These findings has been applied to attempts to identify therapies for adenomyosis based on targeting the vasculature, but the existence of a link between the two conditions is under question for several reasons: only case reports (or very small series) have been published; all published cases come from one region of the world (the Far East); the published literature does not contain objective proof of a causal relationship between the two pathologies, except for the elevation of some markers. In summary, it is not possible to conclude that the presence of adenomyosis has a pathogenetic role in causing vascular events, first and foremost because available evidence consists mostly of case reports.

Reproductive Medicine doi: 10.3390/reprodmed6040037

Authors: Cristina-Diana Popescu Romina Marina Sima Mircea-Octavian Poenaru Ancuta-Alina Constantin Gabriel-Petre Gorecki Andrei-Sebastian Diaconescu Mara Mihai Cristian-Valentin Toma Liana Pleș

Objectives: Female fertility is increasingly threatened by environmental pollutants such as fine particulate matter (PM2.5 and NO2), endocrine-disrupting chemicals (BPA, phthalates, PFAS, and PCBs), and microplastics. These exposures are associated with impaired ovarian reserve, reduced implantation rates, and lower assisted reproductive technology (ART) success. Given the rising prevalence of obesity and weight-loss interventions, particularly bariatric surgery, understanding the combined influence of metabolic and environmental factors on reproductive outcomes is of critical importance. This review aimed to synthesize recent evidence on how these exposures interact to affect female fertility. Methods: A narrative review was conducted of studies published between 2019 and 2025 using PubMed, Google Scholar, Web of Science, and Wiley Online Library. The PubMed Boolean search string was “female fertility”, “ovarian function”, “IVF” and “pollution”, “endocrine disruptors”, “air pollutants”, and “microplastics”. Searches were limited to English language publications, with the last search performed on 30 March 2025. Human, animal, and in vitro data were screened separately. Human evidence was prioritized, and confounding factors (age, BMI, and smoking) were considered during interpretation. Results: Environmental pollutants were consistently associated with diminished ovarian reserve, poor oocyte quality, and reduced live birth rates in ART. PFAS exposure correlated with lower fecundability, while PM2.5 and NO2 were linked to decreased AMH and AFC levels. Mechanistic animal and in vitro studies support these findings through pathways involving oxidative stress, endocrine disruption, and epigenetic alterations. Rapid metabolic changes, particularly post-bariatric surgery, may transiently increase circulating lipophilic toxicants and reduce antioxidant defenses, amplifying reproductive vulnerability. Conclusions: Environmental exposures, especially PM2.5, NO2, PFAS, and microplastics, adversely influence ovarian and embryonic competence. Rapid metabolic transitions may further modulate this susceptibility through pollutant mobilization and micronutrient imbalances. Future interdisciplinary prospective studies integrating exposure monitoring, metabolic profiling, and reproductive endpoints are essential to guide clinical recommendations and precision fertility counseling.

Reproductive Medicine doi: 10.3390/reprodmed6040036

Authors: Dagna Karakaite Jelena Volochovic

Background and Clinical Significance: This article presents a clinical case of persistent umbilical vein of the extrahepatic type in a fetus. The features, diagnosis, and prognosis of this rare vascular anomaly, as well as the applied pregnancy monitoring tactics, are reviewed. Case Presentation: A 34-year-old woman was referred to a tertiary-level hospital at 25th weeks’ gestation for evaluation of a suspected fetal heart defect. Persistent right umbilical vein of the extrahepatic type, cardiomegaly with predominant atrial enlargement, a primum atrial septal defect, and hydropericardium were diagnosed. At 33 + 5 weeks of gestation, signs of decompensation emerged, including progressive cardiomegaly, hydropericardium, and newly developed ascites, leading to the decision to induce labor. Imaging was performed using a Voluson E8 ultrasound system (GE Healthcare, Zipf, Austria). Despite all efforts, the severity of the condition ultimately proved fatal in this clinical case. Conclusions: Patients carrying fetuses suspected or diagnosed with PRUV should receive coordinated management by a multidisciplinary team of specialists. Delivery should be planned in a tertiary-level hospital.

Reproductive Medicine doi: 10.3390/reprodmed6040035

Authors: Rachael Sampson Patricia Rojas Mendez Viren Kaul

Background/Objectives: There is a paucity of research studying point-of-care ultrasound in the pregnant population, despite the rising incidence of maternal medical complications and, in particular, preeclampsia. This study sought to compare the inferior vena cava collapsibility index (IVC-CI) between patients with preeclampsia with severe features (PECS) and gestational age-matched controls and to assess whether pulse pressure (PP) correlates with IVC-CI in PECS. Methods: This was a prospective pilot study of patients recruited at an inpatient hospital and an outpatient office. The case group included admitted patients with a diagnosis of PECS considered to be stable for prolonged antepartum expectant management. One patient per gestational age week from 23 to 34 weeks with PECS was compared to a gestational age-matched patient without any form of preeclampsia and/or gestational hypertension. Patients on magnesium sulfate, those with multiple gestation, large-for-gestational age fetus, fetal growth restriction, polyhydramnios, oligohydramnios, and/or an anomalous fetus were excluded. Results: IVC-CI was significantly lower in the PECS group compared with controls (mean 20.1% vs. 48.3%, 95% CI = −0.40–−0.16, p < 0.001). There was an inverse relationship between IVC-CI and pulse pressure in patients with PECS. For each additional 1 mmHg in pulse pressure, the odds of having IVC-CI greater than 50% decreased by 13%. Conclusions: Patients with preeclampsia exhibit detectable changes in inferior vena cava diameter that can be assessed with bedside ultrasound and correlated with maternal PP. Future research should focus on validating these findings and exploring the clinical significance of these measurements.

Reproductive Medicine doi: 10.3390/reprodmed6040034

Authors: Shajna Kinarulla Kandi Osama Oro Shareef Abdelrahim Obeid Mandy Abushama Badreldeen Ahmed Justin C. Konje

Background: Infertility is a multifactorial condition that causes significant emotional distress and financial burden for couples. Despite advances in assisted reproductive technologies (ARTs), many patients experience recurrent implantation failure (RIF) or pregnancy loss. Intralipid, an intravenous lipid emulsion, has been proposed as an adjunctive therapy due to its immune-modulatory effects, particularly in reducing elevated natural killer (NK) cell activity, which may be associated with poor reproductive outcomes. This study evaluated the effect of intralipid infusion on pregnancy rates and miscarriage rates in women with recurrent implantation failure undergoing in vitro fertilization (IVF). Materials and Methods: This was a retrospective study of women who had suffered from recurrent implantation failure and underwent IVF between September 2023 and September 2024. A comparative group undergoing IVF but who did not have recurrent implantation failure matched for age was selected. Outcomes of clinical pregnancy, miscarriage and livebirth rates were compared in both groups. Results: A total of 113 women undergoing IVF were identified and 51 received intralipid. Intralipid was initiated at varying stages of the IVF process, a day before embryo transfer (ET) (18 or 35.3%), on the day of ET (20 or 39.2%) and after ET (13 or 25.5%). The clinical pregnancy rate was 44.2% in the treatment group compared to 29% in the comparator group (p < 0.05) while the miscarriage rates were 13.7% versus 11.3% (p > 0.05). Elevated NK cells were present in 65.4% of the patients who received intralipid, but the correlation between NK cell levels and pregnancy outcomes was weak (Spearman ρ = 0.032). No adverse effects were reported in any of the women. Conclusions: Intralipid infusion increased the successful pregnancy rates in women who had recurrent implantation failure during IVF. The successful pregnancy rate was significantly higher than that in those undergoing ART who had not suffered from RIF. These findings support several studies on the potential benefit and safety of intralipids in women undergoing ART, but the numbers remain small and more prospective studies are needed to confirm these findings

Reproductive Medicine doi: 10.3390/reprodmed6040032

Authors: Viorela-Romina Murvai Anca Huniadi Radu Galiș Gelu Florin Murvai Brenda-Cristiana Bernad Carmen Ioana Marta Timea Claudia Ghitea Ioana Cristina Rotar

Introduction: Maternal thrombophilia is associated with numerous obstetric complications, often occurring without overt clinical manifestations during pregnancy. Histological evaluation of the placenta can provide valuable insights into the etiology of these complications. Objective: To compare the placental histopathological profile in pregnancies with thrombophilia versus physiological pregnancies and to develop a synthetic score capable of retrospectively indicating thrombophilic risk. Materials and Methods: A retrospective observational study was conducted on two groups (n = 80 thrombophilia, n = 31 control). Macroscopic and histopathological placental parameters were analyzed. A histological score (range 0–5 points) was constructed based on the presence of villous stasis, stromal fibrosis, infarction, acute atherosis, and intervillous thrombosis. Results: The mean histological score was significantly higher in the thrombophilia group (2.20 ± 1.4) compared to the control group (1.18 ± 1.1; p = 0.0011). A score ≥ 3 was present in 39.1% of thrombophilic cases versus 13.6% in controls. Regression analysis showed that only placental diameter was significantly correlated with the histological score (p = 0.0379). Conclusions: The proposed histological score may serve as a simple and effective tool for the indirect identification of potential thrombophilic risk in complicated pregnancies. Its validation in future studies could support its implementation in routine obstetric and histopathological practice.

Reproductive Medicine doi: 10.3390/reprodmed6040033

Authors: Rebecca Rachel Zachariah Susanne Forst Nikolai Hodel Verena Geissbuehler

Background/Objective: Dyspareunia negatively affects women’s lives. Up to 35% suffer from postpartum dyspareunia. Many factors may influence the occurrence of postpartum dyspareunia, but little is known about them. This study aimed to look at the frequency of dyspareunia one year postpartum in a cohort of primiparae. Which perinatal factors influence the frequency of postpartum dyspareunia? Methods: A total of 3264 primiparae were included in this observational cohort study. Perinatal factors were documented, and a specially designed questionnaire was sent to them one year postpartum. The primary outcome was the frequency of dyspareunia one year postpartum. The secondary outcomes included potential influencing factors such as birthing method (spontaneous bed delivery, spontaneous delivery other than bed, water delivery, and vacuum-assisted delivery); perineal injuries (first- and second-degree perineal tears, obstetric anal sphincter injuries (OASIs), and episiotomies); and the use of oxytocin. Results: Postpartum dyspareunia was observed in 15% of the 3264 primiparae. In multivariate analysis, there were influences found in the perineal injury group, especially for first- and second-degree perineal tears and OASIs. In the oxytocin group, a trend toward a higher rate of postpartum dyspareunia was observed. No influence of the different birthing methods was found. Conclusions: Postpartum dyspareunia, affecting 15% of women one year after vaginal delivery, is associated with perineal injuries, particularly minor perineal tears and OASIs. This highlights the importance of good preparation of the perineum and pelvic floor before delivery, efficient perineal protection during labor, and the use of a precise repair technique for all perineal injuries.

Reproductive Medicine doi: 10.3390/reprodmed6040031

Authors: Martiniuc Ana-Elena Laurentiu-Camil Bohiltea Pop Lucian Gheorghe Suciu Nicolae

Background: The human fetal adrenal gland is a unique endocrine organ with distinct morphology and functional dynamics, which is significantly different from the postnatal adrenal. Its rapid growth and vital steroidogenic role during gestation have positioned it as a key regulator of fetal development and pregnancy maintenance. Objectives: To provide a comprehensive overview of the morphogenesis, function, regulatory mechanisms, and clinical implications of the human fetal adrenal gland, highlighting recent advances in understanding its development and its role in prenatal and postnatal health outcomes. Methods: A systematic review was conducted, including original research articles focused on human fetuses or validated animal models, examining the genetic, molecular, and hormonal mechanisms underlying adrenal development and function. Studies were excluded if they were editorials, case reports, focused on adult adrenal physiology, had small sample sizes, or were non-English publications. Study quality was evaluated using PRISMA guidelines. Results: The fetal adrenal gland develops from both mesodermal and ectodermal origins, forming three primary zones: fetal, transitional, and definitive. Each zone has distinct functions and developmental pathways. The fetal zone, which predominates, is responsible for producing dehydroepiandrosterone sulfate, DHEA-S, which is crucial for placental estrogen synthesis. The adrenal gland undergoes rapid growth and functional maturation, regulated by ACTH, placental CRH, IGF, and the renin–angiotensin system. Disruption of adrenal function is associated with conditions such as preterm birth, adrenal hypoplasia, congenital adrenal hyperplasia, and intrauterine growth restriction. Emerging evidence suggests that fetal adrenal hormones may influence long-term health through fetal programming mechanisms. Conclusions: The fetal adrenal gland plays a critical and multifaceted role in fetal and placental development. This gland influences placental development via steroid precursors (DHEA-S → estrogen synthesis), while also being regulated by placental factors such as the corticotropin-releasing hormone. Understanding its complex structure–function relationships and regulatory networks is essential for predicting and managing prenatal and postnatal pathologies. Future research should focus on elucidating molecular mechanisms, improving diagnostic tools, and exploring long-term outcomes of altered fetal adrenal function.

Reproductive Medicine doi: 10.3390/reprodmed6040030

Authors: Zahi Hamdan Rhianon Bou Deleh Joenne Al Khoury Somar Soufan Rafi Haddad Emile Dabaj Sami Azar Hilda E. Ghadieh Marouan Zoghbi

Telemedicine has emerged as a promising tool in obstetric and reproductive healthcare, offering new possibilities for patient-centered care delivery. This literature review explores its impact across key areas, including abortion, assisted reproduction, childbirth, contraception, gestational diabetes, mental health, opioid and smoking cessation, and perinatal care during the COVID-19 pandemic. A structured narrative approach was applied, with studies identified through PubMed and Scopus databases for screening, with selection based on predefined inclusion and exclusion criteria, and synthesized narratively with attention to clinical outcomes, access, satisfaction, and barriers to implementation. Perspectives on the acceptance of telemedicine among healthcare providers, technological advancements enhancing reproductive outcomes, and telemedicine’s pivotal role in maintaining continuity of care during crises, such as the COVID-19 pandemic, are examined. The review also addresses challenges and barriers, including technological proficiency and patient acceptance, while emphasizing telemedicine’s potential to improve accessibility, patient satisfaction, and healthcare outcomes across diverse reproductive health services.

Reproductive Medicine doi: 10.3390/reprodmed6040029

Authors: Inês Carrilho Melissa Mariana Elisa Cairrao

Background/Objectives: Classified as a hypertensive disorder of pregnancy, preeclampsia is one of the leading causes of maternal and fetal morbidity and mortality. The abnormal trophoblast invasion that leads to a failed transformation of the uterine spiral arteries during placentation remains the most probable cause for preeclampsia. It is known that adiponectin acts on the placenta, playing a regulatory role in placentation processes. Therefore, the aim of this systematic review is to compile scientific evidence to evaluate the role of adiponectin as a biomarker for preeclampsia. Methods: The protocol for this systematic review was registered on the PROSPERO database (ID CRD42024542403) and follows the PRISMA 2020 guidelines. Overall, twenty-nine studies were selected from the PubMed and Scopus databases, including case–control, prospective and retrospective cohort, cross-sectional, and bidirectional Mendelian randomization studies. Results: From the articles analyzed, nine studies indicated an increase in adiponectin levels in preeclampsia, eleven reported a decrease, eight detected no significant changes, and in two studies, it was not possible to determine the glycoprotein levels. Analysis of the evidence quality revealed that moderate and low evidence levels predominate, with stronger evidence for decreased adiponectin levels. Conclusions: Promoting the advancement of scientific research is crucial, particularly exploring the association between adiponectin and other biomarkers. This approach could facilitate the development of screening and diagnostic methods, enabling the implementation of specific preventive and therapeutic strategies.

Reproductive Medicine doi: 10.3390/reprodmed6040028

Authors: Amelia C. Inclan Danielle Snyder Sophie G. Tillotson Katelyn E. Flaherty Angelica Byrd Alyssa Pasvantis Charlotte Chaiklin

Primary care providers are increasingly tasked with providing basic gynecologic care, including contraceptive therapy, to their patients. In the United States, oral contraceptive pills are the most frequently prescribed form of contraception; thus, it is critical that primary care providers are well versed in addressing common patient questions. Well-documented concerns relating to oral contraception initiation include changes in weight, mood, cancer risk, libido, acne, and infertility. Herein, we provide a clinical case example of a patient with these common concerns, review the related evidence, and suggest appropriate counseling with the goal of helping primary care clinicians provide the highest level of evidence-based oral contraceptive care.

Reproductive Medicine doi: 10.3390/reprodmed6040027

Authors: Raffaele Tinelli Federica Savasta Stefano Angioni Giorgio Bogani Livio Leo Alessandro Messina Alessandro Libretti

Background: Cornual pregnancy (CP) is a rare but life-threatening form of ectopic pregnancy. Severe complications include uterine rupture and massive hemorrhage, often requiring complex surgical management despite prompt intervention. We report a case of a ruptured left CP at 12 weeks, occurring three months after ipsilateral salpingectomy for a tubal pregnancy. Case Presentation: A 27-year-old woman, gravida 2, with a history of left salpingectomy, presented at 12 weeks of amenorrhea with severe pelvic pain and irregular uterine bleeding. Clinical examination, serum β-hCG testing, and transvaginal ultrasound confirmed hemoperitoneum due to rupture of a cornual pregnancy. Emergency laparoscopy was performed, with drainage of massive hemoperitoneum, excision of the ectopic gestation, and uterine wall repair. Uterine integrity was preserved, and the patient was discharged without complications. Discussion: Cornual ectopic pregnancy remains diagnostically and surgically challenging, with high risk of catastrophic hemorrhage. Transvaginal ultrasonography, supported by 3D ultrasound or MRI in equivocal cases, facilitates early diagnosis. Laparoscopy is increasingly recognized as the gold standard, offering reduced morbidity, faster recovery, and preservation of fertility compared with laparotomy, though it requires advanced surgical expertise. Long-term follow-up is essential due to the risk of uterine rupture in subsequent pregnancies, and elective cesarean delivery is often advised. Conclusion: This case demonstrates that minimally invasive laparoscopic management of ruptured CP with massive hemoperitoneum is feasible and safe when performed by experienced surgeons, but further studies are needed to optimize standardized protocols and assess reproductive outcomes.

Reproductive Medicine doi: 10.3390/reprodmed6040026

Authors: Ingrid Dravecká

Pregnancy in women with type 1 diabetes mellitus (T1DM) is associated with a high risk of maternal and perinatal complications, and achieving optimal glycaemic control remains a clinical challenge. This article presents a narrative review of the evidence on advanced hybrid closed loop (AHCL) insulin delivery systems in pregnancy, with a focus on maternal glycaemic outcomes, neonatal outcomes, and psychosocial aspects. The relevant literature was identified through a structured search of PubMed, Scopus, and Web of Science (2010–2025), supplemented by guideline documents and reference screening. Eligible studies included randomised controlled trials, observational studies, and qualitative investigations. Data were synthesised thematically. Findings from key trials, including CONCEPTT, AiDAPT, and CRISTAL, demonstrate that AHCL systems improve time in range, lower mean glucose, and reduce hyperglycaemia without increasing hypoglycaemia. Some evidence also suggests improved neonatal outcomes, though statistical significance varies. Qualitative studies highlight reduced anxiety, improved sleep, and enhanced quality of life for women using AHCL during pregnancy. In conclusion, AHCL systems show strong promise in optimising maternal glycaemic control and potentially improving perinatal outcomes. However, larger, unbiased studies and real-world evaluations are needed to confirm their benefits and support broader clinical implementation.

Reproductive Medicine doi: 10.3390/reprodmed6030025

Authors: Alessandro Messina Alessio Massaro Eleonora Dalmasso Ilaria Giovannini Giovanni Lipari Paolo Alessi Tiziana Bruno Sofia Vegro Daniela Caronia Federica Savasta Valentino Remorgida Alessandro Libretti Bianca Masturzo

Background/Objectives: Outpatient operative hysteroscopy is a cornerstone in the management of intrauterine pathologies within reproductive medicine. However, procedural pain and anxiety remain key barriers leading to failed procedures and referrals for surgery under general anesthesia. This study aimed to assess whether a comfort-enhanced procedural environment could reduce perceived pain and increase procedural success rates. Methods: Analysis of 970 consecutive patients who underwent outpatient operative hysteroscopy at the Hysteroscopy Unit of “Degli Infermi” Hospital (Biella, Italy): 470 in 2023 under standard conditions, 500 in 2024 with an enhanced setting. Surgical technique, analgesic/sedation policies and operators were unchanged. The primary outcome was referral to the OR for completion of the procedure. Secondary outcomes included patient-reported pain assessed by Visual Analog Scale (VAS) in a consecutive subsample. Differences between years were evaluated with appropriate parametric/non-parametric tests. Results: Implementation of the enhanced environment was associated with a lower OR referral rate in 2023 versus 2024. Post hoc power for this comparison was approximately 60%. Mean VAS scores also decreased in 2024, with post hoc power >99%. No adverse events were recorded. Conclusions: Environmental and interpersonal modifications were associated with meaningful decline in reported pain and OR referrals. Prospective studies incorporating systematic case-mix and validated anxiety measures are warranted to confirm these results.

Reproductive Medicine doi: 10.3390/reprodmed6030024

Authors: Alyona Chernyshova Michael Krylyshkin Alexander Chernyakov Julia Truschuk Ekaterina S. Marchenko Sergey Fursov Olga Tkachuk Svetlana Tamkovich

Objectives: The aim of this study is to demonstrate the efficacy of the modified technique of radical organ-preserving surgery of invasive cervical cancer (CC) in patients of reproductive age. Methods: This study included 118 patients of reproductive age (34.9 ± 4.8 years) with a morphologically verified diagnosis of invasive CC (T1a-1bNxM0). All patients underwent organ-preserving surgery in the scope of radical trachelectomy. A shape memory mesh implant woven in the form of a stocking from superelastic nickelide titanium thread with subsequent fixation with separate sutures around the perimeter was used to form the uterine closure apparatus and to strengthen the utero-vaginal anastomosis. The mesh implant was made of superelastic thin nickelide titanium threads with a diameter of 60–40 microns on a metal knitting machine. All patients were prospectively followed up for a mean of 120 months. Results: No intraoperative or postoperative complications were revealed when using a shape memory implant made of titanium nickelide during radical trachelectomy to form a locking apparatus and strengthen the anastomosis zone. No cervical stenoses or mesh failures were noted in any case. The 5-year overall and recurrence-free survival rates were 100% and 98%, respectively. Two patients indicated recurrence; it occurred in 3 and 36 months. There were 42 spontaneous pregnancies, and 29 resulted in full-term delivery, whereas 2 and 11 ended in miscarriage and early abortion, respectively. Currently, 18 patients are at different stages of the use of assisted reproductive technologies. Conclusions: The shape memory implant made of titanium nickelide integrates well into the surrounding tissues and successfully imitates the effect of the cervix. The use of this sparing-surgery technique has shown reasonably good results in carrying the pregnancy to term and good reproductive outcomes.

Reproductive Medicine doi: 10.3390/reprodmed6030023

Authors: Anna E. Reinert Maria Bolshakova Alexander S. Wong Victoria K. Cortessis

Background/Objectives: Legal access to cannabinoids is increasing, and patients with chronic pelvic pain from endometriosis were hypothesized to explore and find benefit from the use of marijuana for symptom management. A survey of women with endometriosis was conducted with the objective of characterizing their experience with marijuana for management of pelvic pain: exploring symptom benefit, characteristics of use, and factors contributing to use and discontinuation. Methods: A descriptive cross-sectional survey was undertaken using an anonymous online questionnaire. Participants were recruited from an outpatient gynecology clinic using endometriosis ICD-10 diagnostic codes, and from the Endometriosis Association mailing list. Results: Marijuana use for symptom relief was reported by 78 (32.2%) Endometriosis Association participants, and 58 (46.8%) clinic participants. Within both populations, marijuana was considered very or moderately effective by most users (68.0 to 75.9%). Legality of recreational and medicinal marijuana in the state of residence was strongly associated with use (OR 7.13 [95% CI: 2.57–19.8]). Among users specifying current or past use, discontinuation was reported by 45% (54 of 121), and most frequently attributed to non-clinical factors of legal/employment risk and obstacles to marijuana access; 64.8% of former users attributed discontinuation to non-clinical factors only. Lack of symptom relief from other clinical management was the most cited motivation for initiation (55.1% clinic, 39.7% EA users). Conclusions: Marijuana use is common among women with endometriosis and chronic, refractory pelvic pain. Legality and access appear to impact use and discontinuation. While legal access to marijuana is associated with increased use, marijuana obtained outside of legal routes is also commonly being used for symptom relief.

Reproductive Medicine doi: 10.3390/reprodmed6030022

Authors: Alessandro Messina Safae El Motarajji Ilaria Giovannini Alessandro Libretti Federica Savasta Valentino Remorgida Livio Leo Bianca Masturzo

Background: Outpatient operative hysteroscopy is a minimally invasive procedure widely used for the diagnosis and treatment of intrauterine pathologies, including intrauterine adhesions (IUAs), which significantly affect fertility. Despite its therapeutic potential, the procedure itself may predispose patients to de novo adhesion formation. This review evaluates the effectiveness of anti-adhesion gels, particularly hyaluronic-acid-based formulations, in preventing IUAs and improving reproductive outcomes after outpatient operative hysteroscopy. Materials and Methods: A systematic search was performed in PubMed, CINAHL, Embase, and Web of Science for studies published between January 2020 and May 2025. Inclusion and exclusion criteria were defined using PICO guidelines. Relevant studies were screened and selected by two independent reviewers. Results: Anti-adhesion gels, especially hyaluronic acid and its derivatives, were associated with a lower recurrence of IUAs and improved reproductive outcomes. Combination therapies, such as hyaluronic acid gel with intrauterine devices (IUDs), showed better efficacy than monotherapy. Several studies also reported increased endometrial thickness, higher implantation rates, and improved pregnancy outcomes, although live birth rates remained inconsistent. Conclusions: Hyaluronic-acid-based anti-adhesion gels appear effective in reducing postoperative adhesion formation and enhancing reproductive outcomes in outpatient hysteroscopy. The best results are seen with multimodal preventive strategies. However, heterogeneity across studies highlights the need for standardized, prospective, randomized controlled trials to establish optimal clinical use.

Reproductive Medicine doi: 10.3390/reprodmed6030021

Authors: Dimitar Cvetkov David Lukanovic Angel Yordanov

Background and Clinical Significance: Cervical ectopic pregnancy (CEP) is a rare and potentially serious condition, in which the embryo implants within the cervical canal rather than the uterine cavity and is present in less than 1% of all ectopic pregnancies. There are different treatment options depending on the particular situation and the woman’s reproductive desire but conservative approaches as the first line of treatment is preferred in all cases and hysteroscopic resection of the fetus is one of these options. Several types of laser systems are available for use in hysteroscopic surgery, including neodymium:YAG (Nd:YAG) lasers, KTP and Argon lasers, as well as diode lasers. The holmium:YAG (Ho:YAG) laser, although more commonly used in urology due to its ability to cut, coagulate, and vaporize tissue, has gained interest in gynecologic procedures because of its precision and favorable safety profile. Case Presentation: We present the case of a 32-year-old woman, pregnant for the first time, who was diagnosed with CEP and successfully treated using a Ho:YAG laser during an outpatient hysteroscopic procedure. As far as we know, this is the first published case using this approach. Conclusions: The Ho:YAG laser is a proven tool for outpatient hysteroscopic procedures like septum and adhesion removal. Its ability to both cut and coagulate offers a minimally invasive, fertility-sparing option for managing cervical ectopic pregnancy. With the right patient and proper backup plans in place, this approach could be a promising alternative to more aggressive treatments.

Reproductive Medicine doi: 10.3390/reprodmed6030020

Authors: Kahibi Bernard Fridolin Mujuni Dismas Matovelo Edgar Ndaboine Richard Kiritta Ladius Rudovick

Background/Objective: Pregnancy-related acute kidney injury (PRAKI) remains a serious complication, with high rates of maternal morbidity and mortality, particularly in developing countries where delayed diagnosis and treatment are common. This study aimed to determine the proportion, associated risk factors, and maternal outcomes among pregnant and postpartum women at high risk of developing AKI. Methods: This cross-sectional analytical study was conducted at Bugando Medical Centre in Mwanza, Tanzania, from May 2023 to February 2024, targeting high-risk obstetric patients. Results: Out of 4588 admissions, 420 patients were identified as being at risk of developing PRAKI. Among them, 101 (24.22%) were diagnosed with PRAKI, while 316 (75.78%) did not develop the condition. The leading associated risk factors were pre-eclampsia (40.59%) and postpartum hemorrhage (PPH) (40.24%), followed by sepsis (11.8%) and abortion-related complications (5.94%). Multivariate analysis revealed that living in rural areas and having a lower level of education were significantly associated with PRAKI. Patients from rural areas had an adjusted odds ratio (AOR) of 5.37 (p < 0.001), while those with informal or primary education had an AOR of 4.21 (p = 0.048). Conclusions: The study also found that maternal mortality was significantly higher among patients with PRAKI, particularly those affected by PPH. These findings highlight the urgent need for improved management of obstetric emergencies to reduce PRAKI incidence and improve maternal outcomes in high-risk populations.

Reproductive Medicine doi: 10.3390/reprodmed6030019

Authors: Alexandra Peyser Cailey Brogan Lilli Zimmerman Randi H. Goldman

Background: Preimplantation genetic testing for polygenic diseases (PGT-P) is a reproductive technology that has made it possible to assign risk scores to embryos for various complex polygenic conditions such as diabetes, hypertension, breast cancer, and schizophrenia. Whether there is public interest in utilizing PGT-P and what public opinions are regarding this technology is unknown. Therefore, the objective of our study was to evaluate the opinion of the general United States (US) public regarding PGT-P. Methods: A web-based questionnaire consisting of 25 questions was administered to a nationally representative sample of adult US residents according to age and sex. The survey contained a description of PGT-P, followed by questions with Likert-scale responses ranging from strongly agree to strongly disagree. Results: Of the 715 respondents recruited, 673 (94%) completed the survey. Most respondents agreed that use of PGT-P is ethical (54%), and another 37% were neutral; however, approximately 9% of respondents disagreed and were opposed to the use of PGT-P. Those that opposed PGT-P cited that it was “unethical” (46%) or “not natural” (39%), believed children could be negatively affected (31%), or stated that it went against their religion (15%). The majority of respondents did not know whether PGT-P was safe for embryos (68%) or children (67%) and felt that anyone should be able to utilize it (53%). Conclusions: Participants who were younger, were Atheist, or were Democrats were more likely to agree that “PGT-P is ethical”. This study identified that more than half of respondents supported the use of PGT-P. However, concerns regarding its safety and ethical implications persist.

Reproductive Medicine doi: 10.3390/reprodmed6030018

Authors: Balázs Vida Richárd Tóth Petra Merkely Nándor Ács Zoltán Novák Boglárka Balázs Lilla Madaras Ferenc Bánhidy Ádám Tabányi Márton Keszthelyi Balázs Lintner

Background: Cervical cancer is the fourth most common malignancy among women, posing significant diagnostic and therapeutic challenges during pregnancy. Case presentation: This case report presents the treatment of a 32-year-old pregnant woman diagnosed with cervical cancer. Following the diagnosis at 7 weeks of gestation, histological and imaging examinations were performed, leading to the initiation of neoadjuvant chemotherapy. Due to the tumor progression noticed under therapy, cesarean section was performed at 29 weeks, immediately followed by radical hysterectomy. Conclusions: The management of cervical cancer during pregnancy necessitates a multidisciplinary approach, based on the patient’s condition, tumor stage, and fetal maturity. This case highlights the limitations and complexities of treating cervical cancer during pregnancy and emphasizes the importance of individualized oncological and surgical planning.

Reproductive Medicine doi: 10.3390/reprodmed6030017

Authors: Archana Ayyar Marian Khalil Maggie Wong Rebecca Chung Kathryn Coyne Joseph Findley Rachel Weinerman Rebecca Flyckt Katelyn Perroz Sofaly Sung Tae Kim

Objectives: To investigate the impact of α-chymotrypsin treatment on sperm recovery rate and total motile sperm count (TMC) in highly viscous semen for intrauterine insemination (IUI) and in vitro fertilization (IVF), particularly in cases of severely low sperm count. Methods: High viscosity was defined by the inability to form a thread exceeding 2 cm from a semen drop after 30 min of incubation at 37 °C with repeated pipetting. Semen samples were treated with 5 mg of α-chymotrypsin for 5–10 min at 37 °C and washed using a 90% gradient solution. A total of 35 patients were included, with comparisons made to the same patients’ prior untreated samples using paired t-tests. Severely low sperm count was classified as TMC below 10 million. Results: Treatment with α-chymotrypsin significantly improved TMC (22.2 million vs. 11.6 million, p = 0.0004) and motile sperm recovery rate (38.9% vs. 16.2%, p = 0.00002). In cases of severely low sperm count, α-chymotrypsin treatment resulted in a marked increase in recovery rate (43.0% vs. 10.0%, p = 0.02) and TMC (5.89 million vs. 1.21 million, p = 0.004). Fertilization using treated samples achieved an 87.8% success rate, with a 56.4% usable blastocyst rate, comparable to standard IVF outcomes (n = 9, average age = 34.9 years). Conclusions: α-chymotrypsin treatment significantly enhances sperm recovery and TMC in highly viscous semen, demonstrating particular efficacy in patients with severely low sperm counts without affecting fertilization or blastocyst rate in IVF.

Reproductive Medicine doi: 10.3390/reprodmed6030016

Authors: Robert Hauffe Michaela Rath Simran Chopra Karin Müller André Kleinridders

Background/Objective: Fertility relies on efficient energy metabolism in gametes, which is largely determined by mitochondrial activity. The mitochondrial chaperone complex HSP60/HSP10 folds the majority of mitochondrial matrix proteins and thus enables proper function and metabolism. Although it is known that mitochondrial dysfunction impacts male fertility through reduced spermatozoa activity, the importance of HSP60 expression for male fertility remains elusive. Methods: We bred male and female Hsp60+/− with wild-type C57BL/6N mice and analyzed alterations in offspring numbers and characteristics. We further determined testes size as well as spermatozoa quality. Results: We show that breeding Hsp60+/− mice shifted the expected genotype ratio in the pups towards wild-type offspring. Additionally, breeding with Hsp60+/− shifts the sex ratio towards male offspring, independent of parental genotype. In males, HSP60 reduction did not alter testis size or volume, but led to a lower proportion of spermatozoa with active mitochondria and a lower velocity of rapid spermatozoa compared to wild-type counterparts. Accordingly, spermatozoa of Hsp60+/− mice exhibited a further decrease in ATP synthase expression. Conclusions: This suggests that reduced mitochondrial function in Hsp60+/− spermatozoa is a selective disadvantage to sperm, motion performance and fertilization, and mitochondrial dysfunction might be a general selective disadvantage to female offspring.

Reproductive Medicine doi: 10.3390/reprodmed6020015

Authors: Veronika Frisova

Chromosomal defects are a significant cause of perinatal death and childhood disability, occurring in 3.6–6.0 per 1000 births in unscreened populations. Common chromosomal defects include trisomy 21, 18, and 13, triploidy, and sex chromosome abnormalities. Screening for these defects began in the mid-1960s with the advent of amniocentesis, and various methods have since been developed to improve screening performance. Initial screening was based solely on maternal and gestational age, a method incorporated later into all subsequent screening methods giving an a priori background risk. This a priori background risk, which is further refined by maternal serum biochemistry, results of ultrasound examinations, and most recently, results of non-invasive prenatal testing by cell-free DNA in maternal blood. This paper will describe methods of screening for all chromosomal defects and their performance. Unlike most reviews, this paper covers not only screening tests for Down syndrome, but also screening methods for the other most common and less common chromosomal defects.

Reproductive Medicine doi: 10.3390/reprodmed6020014

Authors: Mihai Lucan Mircea Sandor Alin Bodog Diana Mocuta Cristina Daniela Aur Liliana Sachelarie Anca Huniadi

Chronic endometritis (CE) is a persistent, often asymptomatic inflammatory condition of the endometrium, increasingly recognized as a potential contributor to infertility and recurrent implantation failure. Despite its clinical significance, CE remains underdiagnosed due to a lack of standardized diagnostic criteria and its subtle clinical presentation. Objective: This review aims to synthesize the current evidence on the pathophysiology, diagnosis, and treatment of CE, highlighting its impact on reproductive outcomes and the effectiveness of therapeutic interventions. A comprehensive literature review was conducted, analyzing 85 peer-reviewed studies published in the last decade, of which 65 were deemed relevant and retained for further analysis. These studies were selected based on their relevance to the pathophysiology, diagnostic methodologies, and treatment outcomes for CE, focusing on their implications for fertility and assisted reproductive technologies (ARTs). The findings suggest that CE is associated with impaired endometrial receptivity, increased inflammatory markers, and reduced implantation and pregnancy rates with ARTs. Histopathological assessment using CD138 immunostaining remains the gold standard for diagnosis, while hysteroscopy and molecular microbiological techniques provide complementary diagnostic value. Antibiotic treatment has been shown to significantly improve implantation rates and pregnancy outcomes, particularly in women with recurrent implantation failure. Emerging therapies, including probiotics and regenerative medicine approaches, are being explored as potential adjuncts to the conventional treatment. Early and accurate diagnosis of CE is essential for optimizing reproductive outcomes. Standardized diagnostic protocols and individualized treatment strategies are crucial for improving implantation success and pregnancy rates in affected women. Future research should focus on refining the diagnostic methods and exploring novel therapeutic options to enhance endometrial health and fertility outcomes.

Reproductive Medicine doi: 10.3390/reprodmed6020013

Authors: Caroline G. Ploeger Kate Hansen Ammon Bayles Adriana Burger Jason Hansen Timothy Jenkins

Background/Objectives: In the past 50 years, human reproductive capacity has steadily declined with elusive and idiopathic origins. Amongst theorized causes, oxidative stress has been proposed to directly contribute to male infertility. The glutathione (GSH) and glutathione disulfide (GSSG) molecular couple reflect cellular redox environments and are thus reflective of oxidative stress in most cells. Shifting GSH/GSSG redox states to abnormal, more oxidizing conditions can disrupt normal cellular activities. This study explores the correlation between the GSH/GSSG redox system and factors involved in male infertility, including sperm quality, specifically sperm motility and total count. Methods: Semen samples from 98 patients underwent high-performance liquid chromatography (HPLC) for GSH/GSSG analysis. A protein assay determined the protein concentration for normalization, and GSH/GSSG redox potentials (Eh) were calculated using the Nernst equation. Results: A significant inverse correlation between GSH/GSSG Eh and sperm count was identified (p = 0.0046 and R2 = 0.071). Analysis also found that cellular GSH concentrations (p < 0.001 and R2 = 0.11) and total GSH (GSH + (GSSG × 2); p = 0.0039 and R2 = 0.074) were significantly and positively correlated with total sperm count, whereas GSSG concentrations were not. The correlation between redox potential and motility was not significantly different (p = 0.11 and R2 = 0.02). Conclusions: This study shows that total sperm count decreases with increasing redox potential, indicating that more oxidized systems, such as the GSH/GSSG system, are associated with lower sperm counts in ejaculated sperm samples. These findings support a potential link between oxidative stress and sperm parameters. As understanding of the relationship between GSH/GSSG Eh and sperm quality improves, this may inform future potential therapies and approaches aimed at supporting male reproductive health.

Reproductive Medicine doi: 10.3390/reprodmed6020012

Authors: Retika Mohan Mena Abdalla Anna-Lucia Koerling Sahathevan Sathiyathasan

Cervical cancer is a significant global health challenge, ranking as the fourth most common malignancy in women worldwide (age-standardized incidence: 13.3/100,000). In the UK, prevalence is markedly lower (7.6/100,000) compared to global averages, attributable to successful HPV vaccination and screening programs. post-treatment follow-up is critical for monitoring recurrence, managing complications, and addressing survivors’ psychosocial needs. However, follow-up care lacks standardization, especially for advanced-stage cervical cancer. This narrative review critically assesses existing guidelines, practices, and innovative approaches to follow-up care post-cervical cancer treatment, identifying inconsistencies and offering recommendations for standardization. This review synthesizes recommendations from 12 guidelines (NCCN, ASTRO, ESGO, BSCCP, BGCS, and ESMO) to evaluate follow-up strategies for cervical cancer survivors. Emerging evidence supports risk-stratified approaches combining Patient-Initiated Follow-Up (PIFU) for low-risk patients with intensive imaging (PET/CT/MRI) for advanced stages. Psychosocial interventions, particularly for sexual health and return-to-work challenges, remain underutilized despite ESGO recommendations. Follow-up recommendations vary significantly, focusing on clinical examination and symptom-based imaging. Patient-Initiated Follow-Up (PIFU) is a growing trend, though concerns persist regarding its appropriateness for high-risk groups. Most recurrences are symptomatic, supporting less-intensive protocols for low-risk patients. Imaging methods like FDG PET/CT provide prognostic insights but are not universally adopted. Psychosocial and psychosexual care needs remain under addressed. Standardized, evidence-based follow-up protocols are essential to address disparities in survivorship care. Holistic strategies incorporating psychosocial support and tailored plans will ensure comprehensive care. This is the first review to integrate NCCN imaging standards with ESGO psychosocial care in a risk-stratified model. Future research should refine PIFU models and imaging strategies to balance resource use with quality care. Critical clinical implications emerge: (1) Risk-stratified follow-up reduces unnecessary imaging by 31% (95% CI 24–38%) in low-risk patients while maintaining 98% 5-year survival; (2) mandatory psycho-oncology referrals (per ESGO guidelines) lower depression rates by 58% (OR 0.59); (3) PET/CT should be reserved for stage IIB+ patients with symptoms, saving EUR 2300 per avoided scan. These evidence-based thresholds enable personalized survivorship care.

Reproductive Medicine doi: 10.3390/reprodmed6020011

Authors: Renata Pajtak Krinal Mori

Background/Objectives: Barbed sutures have been recognised to offer numerous advantages compared to traditional sutures in minimally invasive procedures including holding tension. However, they are also associated with increased reports of small bowel obstructions (SBOs) in laparoscopic procedures. We are the first to conduct a review on the incidence of SBOs secondary to the use of barbed sutures in robotic surgery. Our aim is to raise awareness about this rare complication and promote early recognition and timely intervention, leading to a reduction in the incidence of severe complications and thereby improving patient outcomes. Methods: A systematic review of the literature was performed by searching the Ovoid Medline, PubMed and Cochrane Databases. After applying our exclusion criteria of articles unavailable in English, seven articles remained. We examined the literature and calculated the median and mean ranges for surgical procedures, time to presentation, symptoms of presentation, type of complications involving the bowel, the type of barbed suture and the additional length of hospital stay. Results: Our systematic review revealed eight cases of bowel obstruction secondary to the use of a barbed suture during robotic surgery. Robotic sacrocolpopexy had the highest complication rate: the median time to presentation was 14 days with vomiting being the most common presenting symptom. Most cases were resolved with a diagnostic laparoscopy and truncation of the barbed suture, and length of re-admission was a median of 4 days. Discussion: The introduction of new devices always carries advantages as well as unfortunate complications. Minimisation of complications through learnt surgical techniques including shortening thread tails and prompt recognition of the complication on re-presentation are key to optimising future patient care. Conclusions: Further prospective trials in this field will be useful to assess the appropriate use of the barbed suture as well as research dedicated to exploring alternate adhesive sutures.

Reproductive Medicine doi: 10.3390/reprodmed6020010

Authors: Gianna T. Le Galen Schauer Yun-Yi Hung Yunjie Li Miranda Ritterman Weintraub Mara B. Greenberg

Background/Objectives: This study examines index pregnancies with histopathological diagnosis of placenta accreta, based on findings of basal plate myometrial fibers (BPMFs) without intervening decidua, and the risk of hemorrhagic morbidity and/or clinically adherent placenta in the subsequent pregnancy. Outcomes were compared between index pregnancies with incidental asymptomatic BPMF findings and those with symptoms based on hemorrhagic and placental factors. Methods: A retrospective cohort study was conducted at a large, integrated healthcare system from 2008 to 2019. All patients with an index finding of BPMF without intervening decidua and subsequent delivery of a live singleton were identified. Index pregnancies with BPMF were categorized as asymptomatic or symptomatic by the absence or presence of hemorrhagic morbidity and/or clinically adherent placenta. Rates of hemorrhagic morbidity and clinically adherent placenta in the subsequent pregnancy were compared among asymptomatic and symptomatic BPMF index pregnancies in bivariate analyses and multivariate models controlling for potential confounders. Results: A total of 140 patients were found to have BPMF and a subsequent delivery of a live singleton. Subsequent hemorrhagic morbidity/adherent placenta occurred in 28% of cases, with a lower incidence in asymptomatic patients (8% vs. 39%, p < 0.0001). Symptomatic BPMF was associated with increased odds of hemorrhagic morbidity/adherent placenta (aOR 10.2, 95% CI 2.7–38.4). Among 71 patients with subsequent placental pathology, 32% had recurrent BPMF, which correlated with higher morbidity compared to those without recurrence or those without placental pathology (61% vs. 40% vs. 9%, p < 0.0001). Conclusions: Incidentally identified BPMF was associated with a lower rate of subsequent hemorrhagic morbidity and/or adherent placenta compared to symptomatic BPMF. Symptomatic BPMF is highly associated with hemorrhagic morbidity and/or adherent placenta in the next pregnancy compared with incidentally identified BPMF, particularly if it is recurrent. These data can inform counseling and management of pregnant individuals with BPMF planning subsequent pregnancies.

Reproductive Medicine doi: 10.3390/reprodmed6020009

Authors: Judith Goh Sum Sum Lo Hannah Krause

Pelvic floor fistulas are abnormal communications between the lower urinary tract and/or anorectum and the female genital tract. Classification systems for female pelvic floor fistulas have existed for over 150 years. At present, there is no consensus on a classification system. Traditionally, classification systems were used for obstetric fistulas. Earlier classification systems were descriptive (small/large/simple/complex) to communicate clinical findings. More recently, classification systems, in particular the Goh and Waaldijk systems, have been tested to predict the outcome of surgical closure and the risk of post-fistula closure urinary incontinence. Conclusions: Features of the fistula may predict outcomes following fistula surgery but other patient features and surgical experience and skill also play a role in the results.

Reproductive Medicine doi: 10.3390/reprodmed6020008

Authors: Yeeshana Ganpat Fiona Campbell

Background/Objective: Preterm births disproportionately affect low- and middle-income countries (LMICs), where evidence-based interventions to improve birth outcomes are lacking. The objective of this study was to systematically review, collate, and synthesize data on low-dose aspirin’s (LDA) effect on the incidence of preterm births in women from LMICs. Materials and Methods: This review included nine randomized controlled trials (RCTs) spanning thirteen LMICs, with 22,545 participants. The intervention group comprised 11,275 participants and the control group comprised 11,270 participants. The relative risk ratios and pooled intervention effects were calculated using Review Manager software, RevMan v5.4.1, with a random effects model. Low-dose aspirin’s effects on five outcomes were analyzed: preterm birth, perinatal mortality, low birth weight, antepartum hemorrhage, and post-partum hemorrhage. The quality of the studies was assessed by the Cochrane risk-of-bias tool and overall quality of evidence, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Two independent authors participated in screening, data extraction, and quality assessment of the included studies. Results: Low-dose aspirin therapy significantly lowered the risks of preterm births (RR 0.91, 95% CI 0.84–0.98, p = 0.02) and perinatal mortality (RR 0.83, 95% CI 0.73–0.94, p < 0.01) in at-risk pregnant women from LMICs. Its effects on low birthweight and ante- and post-partum hemorrhages were less conclusive. Conclusions: Targeted LDA therapy should be considered to reduce preterm births in at-risk pregnant women from LMICs.

Reproductive Medicine doi: 10.3390/reprodmed6010007

Authors: Philip E. Idaewor Peter Ozua Rotimi A. K. Jaiyesimi Abdalla SAAD Abdalla Al-Zawi

Background/Objective: Actinomyces is a genus of anaerobic gram-positive bacteria. It forms part of human body microbiota commonly in the oral cavity and genital tract. During pregnancy, the organism may cause the rare chorioamnionitis, where the maternal genital tract or other sites such as the oral cavity will be the likely source of the pathogen. This condition may increase the risk of foetal morbidity and mortality, and preterm birth. Methods: The placenta of a 33-year-female, primigravida, who presented with preterm labour and eventual delivery of baby at 20 weeks gestation was sent for histopathological examination. Her antenatal and clinical history were reviewed, to identify possible aetiology for her preterm birth. Results: She is noted to have presented with sudden per-vaginal creamy coloured discharge with no associated odour and no irritation. The discharge became blood staining associated with labour pain, this followed by premature spontaneous rupture of membrane and pre-mature labour. Laboratory tests revealed leucocytosis, neutrophilia, monocytosis, high CRP and elevated derived fibrinogen. The patient was delivered of a live male baby weighing 0.35 kg, who died shortly after birth. Placenta microscopic examination revealed patchy severe acute chorioamnionitis and prominent clusters of Gram-positive filamentous bacteria with histopathologic features of Actinomyces spp. The mother before discharged was treated with oral antibiotic. Conclusions: The intrauterine Actinomyces spp. infection is associated with preterm birth and neonatal mortality, early diagnosis during ante-natal could perhaps prevent preterm birth and reduce the associated neonatal mortality.

Reproductive Medicine doi: 10.3390/reprodmed6010006

Authors: Giulia Fontana Micaela Fredi Cecilia Nalli Rossana Orabona Brunetta Guaragni Laura Picciau Valeria Cancelli Laura Andreoli Sonia Zatti Angela Tincani

Background/Objectives: Evans’ syndrome (ES) is a rare autoimmune disorder characterized by the simultaneous or sequential onset of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Given its rarity, available data concerning the clinical course and optimal management in pregnancy are limited. Methods: We present the case of a 32-year-old woman who experienced ES during her first pregnancy. She had been previously diagnosed with childhood-onset SLE at the age of 14 but had been in treatment-free remission since the age of 24. The treatment of both AIHA and ITP included intravenous immunoglobulins, cyclosporine-A, high dosage oral corticosteroids, and, in the second trimester, rituximab. The delivery was planned at 34 + 6 weeks of gestation (GW); no immunological alterations or infectious complications were detected in the newborn. The post-delivery period was uncomplicated, and the mother was discharged with a normal blood count. A narrative review of available ES cases during pregnancy is also presented. Results: A total of 16 patients with ES in pregnancy were reported, including the one we described. None of them developed major bleedings during gestation, while a case of abruptio placentae with delayed postpartum hemorrhage occurred. ITP was difficult to treat in 4/16 women after delivery; 4/16 patients also developed gestational hypertensive disorders. Perinatal outcomes include 13/17 healthy newborns and 4/17 stillbirths (2 of them were twins), of which 1 was due to fetal AIHA. Gestational age at birth was before 37 GW in 8/17. In 15/16 women, ES resolved after delivery. Conclusions: The occurrence of ES during pregnancy has been rarely reported; it constitutes a clinical challenge due to the need for multiple treatments, including conventional immunosuppressants and/or biologic drugs as steroid-sparing agents. After delivery, ES appeared to be less resistant to treatment than it was during pregnancy.

Reproductive Medicine doi: 10.3390/reprodmed6010005

Authors: Britteny Randall Eric Schmitt Blaine McGraw Donald Gloeb Matthew Blattner

Background and Clinical Significance: Anti-Leucine-rich glioma inactivated-1 (anti-LGI1) encephalitis is a rare, autoimmune disorder often presenting with limbic encephalitis. The reported incidence of anti-LGI1 is 0.83/million/year, with elderly males accounting for the overwhelming majority of cases. While anti-LGI1 encephalitis is a well-known cause of autoimmune encephalitis in men over 50, our literature review found no published cases in pregnant women. The purpose of this study is to describe a rare presentation of this pathology in an unexpected population. Case Presentation: A 21-year-old gravida 2, para 1001 woman at 20 weeks’ gestation presented with worsening seizure-like activity for the past four months, frequent falls, loss of consciousness, and concern for trauma to the abdomen. Her neurologic workup one month prior revealed a 72 h electroencephalography (EEG) with epileptic seizures of the left frontotemporal region, but a normal magnetic resonance image (MRI) of her head. A repeat MRI during this hospitalization showed bilateral limbic and basal ganglia T2 hyperintensities. She was treated with increasing doses of antiepileptic drugs without improvement and was transferred to a neurology intensive care unit, where she was diagnosed with anti-LGI1 encephalitis. She was initially treated with oral corticosteroids with inadequate response, then with intravenous immunoglobulin therapy (IVIG). Her seizure activity persisted throughout her pregnancy, requiring multiple admissions for IVIG, but she eventually delivered a healthy baby and continues to receive long-term care for her new diagnosis. Conclusions: This case illustrates classic findings of anti-LGI1 encephalitis in a non-classic patient population. Knowledge that such a case exists may serve to broaden the differential diagnoses when physicians are presented with a similar pregnant patient and expand the reported patient population in this rare disease.

Reproductive Medicine doi: 10.3390/reprodmed6010004

Authors: Maya Fisher Christine McGough Janelle P. Darby

Background and Clinical Significance: Borderline ovarian tumors (BOTs) are a rare diagnosis, especially in the adolescent population. This can make initial management and surveillance strategies difficult, given the limited guidelines and experience in this young age group. Case Presentation: We present two cases of recurrent serous BOTs diagnosed in adolescent patients. Both patients were initially treated with fertility-sparing surgery and followed with transabdominal pelvic ultrasounds. Secondary surgical debulking of recurrent disease with uterine preservation was successful in both patients with a long-term disease-free status. Conclusions: Although rare, BOTs can occur in adolescent patients and should be on the differential for ovarian masses in this age group. Fertility-sparing surgical techniques, reproductive endocrinology consultation, surveillance strategies, and hormone replacement therapy should all be taken into consideration when treating adolescent patients with BOTs.

Reproductive Medicine doi: 10.3390/reprodmed6010003

Authors: Eric Schmitt Krystal Glasford Samantha Carson Christopher Rosemeyer

Background: Diagnoses for right lower quadrant pain in women must include both gynecologic and non-gynecologic causes. In this differential, ovarian torsion and appendicitis are both serious etiologies that can require swift surgical intervention. Ovarian torsion is the least common of the two, accounting for 2.7% of emergency surgery cases according to a 10-year review, while the lifetime risk of appendectomy for females is 23.1%. As many as 2–3% of patients undergoing surgery for acute appendicitis are instead found to have ovarian torsion. However, there are currently only rare case reports of these two conditions co-presenting in the same patient simultaneously, with little discussion on how to be better prepared before entering the operating room. Objective: The purpose of this study is to describe this rare co-presentation to better inform providers of this potential complication and to improve future patient care outcomes. Method: A case report of a patient seen at Tripler Army Medical Center, Honolulu, Hawaii, was assessed. Conclusions: This case shows the rare possibility of dual acute etiologies of abdominal pain warranting urgent surgical management. This case also highlights the need for a multidisciplinary approach in the pre-procedural evaluation of possible competing etiologies of acute abdominal pain that warrant surgical management. Additionally, this case brings up interesting ethical questions regarding informed consent, autonomy, and the obligation of intraoperatively consulted surgeons to provide definitive and indicated surgical care in the absence of prior discussion of possible pathology.

Reproductive Medicine doi: 10.3390/reprodmed6010002

Authors: Gabrielle J. Ezell Nicolina Smith Mary Condon Katherine Joyce John Joseph Kylie Springer D’Angela S. Pitts

Background/Objectives: In the postpartum period, approximately 12% of patients seek care in the emergency department (ED), with a higher representation of Black patients. Hypertension is a common reason for ED visits during this period, often leading to dangerously delayed diagnosis and treatment. Objective: This study aims to assess the time to diagnosis and treatment of hypertensive disorders in the postpartum period in the ED, focusing on potential disparities in care, to identify areas for quality improvement. Design: Retrospective cohort study. Setting: A multi-centered large medical institution in the metro Detroit area. Methods: Postpartum patients (day 2 through day 28) presenting to the ED from November 2015 to December 2022. Exposures: none. Main Outcome Measures: Primary analysis assessed the time elapsed between severe-range blood pressure readings (greater than/equal to 160 systolic and/or 110 diastolic) and the administration of antihypertensives. Secondary analyses assessed the presence of essential laboratory workups such as complete blood counts, complete metabolic panels, and urine protein and creatinine. Results: Among the 430 women who presented to the ED during the postpartum period with hypertension, 372 (86.5%) exhibited severe-range blood pressure (greater than/equal to 160 systolic and/or 110 diastolic). Patients presented on average on postpartum day 6. Of the patients with severe hypertension, only 72% received a complete blood count, 66% underwent evaluation of creatinine and liver profile, and 4% had a urine protein and creatinine test ordered. The average time from severe-range blood pressure reading to antihypertensive administration was 189 min for Black patients and 370 min for White patients. There were no statistically significant differences in the time of the first blood pressure reading, laboratory evaluation, or treatment of severe-range blood pressure between racial groups. Conclusions: This study identifies the most significant area for improvement in the timely administration of antihypertensive medication following severe-range blood pressure readings. Additional areas for improvement were observed in ordering essential laboratory tests to assess the severity of preeclampsia. The institution demonstrated delayed yet equitable care for White and Black patients, contrary to the existing literature indicating potential racial disparities. A targeted quality improvement plan has been implemented to improve the identified areas of concern to adhere to the ACOG’s treatment recommendations for hypertensive disorders of pregnancy. The impact on patient care will be reassessed at the 1-year mark.

Reproductive Medicine doi: 10.3390/reprodmed6010001

Authors: Michelle Joy Wang Megan V. Alexander Akanksha Srivastava Diana Abbas Sara Young Swetha Tummala Lindsey Claus Ronald Iverson Ashley Comfort Christina D. Yarrington

Background/Objectives: Previous literature has described that non-white pregnant patients are at increased risk of severe morbidity from obstetric hemorrhage (OBH). Here, we investigate whether such disparities are secondary to delay in the administration of postpartum oxytocin for non-white patients compared to white patients. Methods: This is a retrospective cohort study of all deliveries from 2018 to 2019, comparing (1) Hispanic white or non-white race (HW/NWR) pregnant people and (2) non-Hispanic white (NHW) pregnant people. Our primary outcome was the time from delivery to the first dose of postpartum oxytocin, and our secondary outcome was the frequency of other hemorrhage interventions. Results: Out of 3832 patients with self-identified race and ethnicity recorded in their patient record, 644 patients identified as NHW, and 3188 patients identified as HW/NWR. We found no difference in time to first dose of postpartum oxytocin (p = 0.51), and there was also no difference in the frequency of other hemorrhage-related interventions. Conclusions: Our study found no delay in the administration of postpartum oxytocin for non-white patients.

Reproductive Medicine doi: 10.3390/reprodmed5040028

Authors: Adriána Goldbergerová Ladislav Kováč Cecília Marčišová Miroslav Borovský Dominika Kotríková Ľubomíra Izáková Ján Mikas Jana Námešná Zuzana Krištúfková Alexandra Krištúfková

Background: The COVID-19 pandemic highlighted the global challenge of inadequate data on SARS-CoV-2’s effects on pregnant women and their infants. In response, Slovakia, along with other countries, launched a nationwide study to assess the incidence, characteristics, and outcomes of SARS-CoV-2 infection during pregnancy. Methods: We conducted a national observational descriptive study of SARS-CoV-2 positive cases among pregnant women from the pandemic’s onset to its conclusion. In collaboration with the Public Health Office of the Slovak Republic, we identified 1184 pregnant women who tested positive for SARS-CoV-2 and contacted them for participation. Results: Among the 240 participating SARS-CoV-2-positive pregnant women, 13 required hospitalizations, with an increased need for intensive care and respiratory support. However, the absolute risk of poor outcomes remained low. Higher maternal age and infection during the third trimester emerged as key risk factors for hospitalization. A symptomatic course was dominant, with fatigue (70%), headache (58%), and fever (56%) as the leading symptoms. While maternal and neonatal outcomes were generally favourable, a slight increase in caesarean sections and preterm births suggests an indirect impact on maternity care. Vaccination during pregnancy correlated with reduced symptoms and no hospitalizations. Elevated CRP levels were common among infected women, while ultrasound findings remained normal. Conclusions: This study offers a multi-dimensional view of pregnancy during the pandemic, capturing both the mother’s personal concerns and the objective insights from prenatal and labour care settings. The findings suggest that most pregnant women with SARS-CoV-2 experience mild to moderate illness, offering reassurance to clinicians about generally favourable maternal and neonatal outcomes while underscoring the need for vigilance in rare severe cases.

Reproductive Medicine doi: 10.3390/reprodmed5040027

Authors: Brinkley Cover Juliana Tovar Omosiuwa L. Enakpene Christopher A. Enakpene

Introduction: A Skene’s gland cyst is a rare gynecological disorder, and the cause of an adult onset is largely unknown. However, periurethral and perineal cystic lesions are common, causing often indistinguishable symptoms. Therefore, accurate diagnosis is crucial because it can significantly alter clinical management. Methods: A 27-year-old woman was gravida 2 para 1 with the onset of a unique, progressively large vulvar mass that began at approximately 6 weeks of gestation. At 22 weeks of gestation, the mass became more symptomatic and measured approximately 9 cm × 7 cm × 6 cm in size, with some areas of excoriation on the lateral surface. Results: The patient had a pelvic MRI without contrast, and it showed that the mass was most likely a giant Skene’s gland cyst. At 24 weeks, the mass was surgically removed under spinal anesthesia and followed by vulvar reconstruction. Histopathology showed a benign cyst lined by transitional and squamous epithelium cells, which was consistent with a benign Skene’s gland cyst. She recovered fully, continued with the pregnancy and delivered vaginally at 39 weeks and 3 days without complications. Conclusions: A case of excoriating giant Skene’s gland cyst in pregnancy that caused significant discomfort to the patient. To this day, there has been no reported literature of a Skene’s gland cyst this large, especially during pregnancy. Hence, Skene’s gland cysts should be part of the differential diagnosis of a large vulvar mass of this magnitude during pregnancy.

Reproductive Medicine doi: 10.3390/reprodmed5040026

Authors: Stephanie Teasdale Natasha Cannon Alison Griffin Janelle Nisbet H. David McIntyre

Background/Objectives: Adverse pregnancy outcomes correlate with blood glucose levels in women with type 1 diabetes (T1DM). There is a gap between the glycaemic targets and the blood glucose control achieved in pregnancy. This study aimed to investigate the impact of an intensive weekly service on glycaemic control compared with our previous care model in pregnancies affected by T1DM. Materials and Methods: This is a retrospective cross-sectional pre/post study comparing measures of glycaemic control in women with T1DM in each trimester of pregnancy in the 12 months before and the 8 months after the commencement of an intensive weekly insulin stabilisation service (ISS). Results: This study utilised data from Dexcom continuous glucose monitoring (CGM) reports to analyse pregnancy-specific glycaemic data (incorporating time in the range of 3.5–7.8 mmol/L). In total, 16 women provided data for 35 trimesters pre-ISS and 17 women provided data for 38 trimesters post-ISS. There was an improvement in pregnancy-specific time in range in trimester 3 following the commencement of the intensive weekly insulin stabilisation service (pre-ISS mean: 49.6%, post-ISS mean: 61.4%, p = 0.042). Similar results were seen when women using hybrid closed-loop technology were excluded, although statistical significance was not reached. It was not possible to assess the effect of the intervention during the first trimester. There were no statistically significant changes in glycaemia in trimester 2. Conclusions: In a small group of pregnant women with T1DM, a clinically significant improvement in pregnancy-specific time in range occurred in trimester 3, but not in trimester 1 or 2, following the introduction of intensive weekly clinical support.

Reproductive Medicine doi: 10.3390/reprodmed5040025

Authors: Alesha White David B. Nelson F. Gary Cunningham

Acute fatty liver of pregnancy (AFLP), although rare, is a potentially fatal obstetrical disorder. It is characterized by acute liver failure of varying degrees with associated coagulopathy that occurs often in the third trimester of pregnancy. The following review discusses the history, etiopathogenesis, and subsequent clinical and laboratory findings that are associated with this disorder. It additionally attempts to aid in differentiating AFLP from other common obstetrical and non-obstetrical diseases with special emphasis on its differentiation from hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. This review also discusses recommendations for delivery and postpartum care with focus on return to baseline and additional life-saving measures that may need to be pursued in the most difficult and refractory cases. Finally, it addresses maternal and perinatal outcomes associated with the disorder and the effect that this disorder can have on future pregnancies.

Reproductive Medicine doi: 10.3390/reprodmed5040024

Authors: Jun Song Caitlin Martin

Endometriosis is a common benign gynecologic disorder associated with infertility and pelvic pain, affecting 6–11% of reproductive-age females, and can frequently lead to the formation of ovarian endometriomas. Mature cystic teratomas are benign ovarian tumors comprising 10–25% of ovarian tumors. Both pathologies are common individually but rarely coexist. The case presented here describes a 49-year-old female presenting with a large composite endometrioma–mature cystic teratoma, a rare occurrence with few documented cases. The patient had a 24 cm × 17 cm × 15 cm adnexal mass identified via imaging, which was surgically removed. Pathology confirmed a composite tumor, with the teratoma encased within the endometrioma. This case underscores the importance of surgical management in complex adnexal masses to obtain tissue for definitive diagnosis and to exclude malignancy. Given the rarity of such coexistence and the challenges in preoperative diagnosis, surgical intervention is crucial for accurate diagnosis and effective management.

Reproductive Medicine doi: 10.3390/reprodmed5040023

Authors: Giulia Mattei Francesco Iaculli Fabiana Carbone Alessandro Mondo Ludovico Muzii

Cervical cancer is one of the leading causes of mortality in women of reproductive age. In recent years, the development of preventive and therapeutic strategies has significantly increased survival rates. While this represents an important medical achievement, it has also raised a major social issue regarding the need to ensure an adequate quality of life for surviving patients. Many of these women are left without their reproductive capacity at an age when their desire for motherhood has not yet been fulfilled. Infertility or subfertility in cancer survivors is actually a growing problem, complicated by the current trend of increasingly delaying pregnancy. The psychological effects of this issue can be devastating, sometimes even more so than the cancer diagnosis itself. Although today fertility-sparing surgeries can ensure excellent reproductive outcomes with minimal oncological risk, obstetric sequelae remain significant, and affected women often require specialized care pathways. Additionally, adequate counselling is still not provided to all patients who cannot access fertility-sparing treatments and who find themselves without hope. Reproductive medicine is therefore facing the modern challenge of offering concrete options to help these patients realize their desire for motherhood. The aim of this article is to provide an overview of the therapeutic options available to young women facing an early- or later-stage diagnosis of cervical cancer.

Reproductive Medicine doi: 10.3390/reprodmed5040022

Authors: Daniela Rodríguez-García Claudio-Alberto Rodríguez-Suárez Héctor González-de la Torre

Background/Objectives: In vitro fertilization (IVF) is an assisted reproductive technique for women and couples experiencing difficulties in achieving a spontaneous pregnancy, often due to stressors that negatively affect fertility. Humor can be beneficial in these stressful situations, helping to reduce symptoms of anxiety and depression. The primary aim was to analyze the effectiveness of laughter therapy in increasing pregnancy rates in women undergoing IVF. The secondary aims were to identify different types of laughter therapy interventions and evaluate their benefits. Methods: A systematic review was conducted using Medline, Web of Science, Scopus, Cinahl, ProQuest and Lilacs, with the search terms “laughter”, “laughter therapy”, “fertilization in vitro” and “fertilization”. Intervention studies published in English, Spanish, or Portuguese were included, with no limits on the date of publication. Studies with other designs, those conducted with animals and grey literature were excluded. The quality of the included studies was assessed using the Joanna Briggs Institute critical appraisal tools. Results: In total, n = 3 studies (1 randomized clinical trial and 2 quasi-experimental) were included, evaluating pregnancy rates and symptoms of depression and anxiety. The interventions included clowns performing magic tricks and interpreting comic situations. Additionally, they incorporated hand clapping, breathing exercises, childlike playfulness, drinking milk, muscle relaxation exercises, candles, and music. Conclusions: This review does not provide clear evidence on the effectiveness of laughter therapy in increasing pregnancy success in IVF. Although it may have some positive effects in reducing symptoms of depression and anxiety, it is important to note that while the reduction of these symptoms may enhance the emotional well-being of patients, it has not been demonstrated to directly lead to an increase in pregnancy rates. Laughter therapy is an innovative, non-pharmacological intervention that is simple, non-invasive, easy to implement and cost-effective; however, the number of available studies is insufficient. More research is needed to provide better and higher-quality evidence using rigorous designs to evaluate this intervention in IVF clinical practice.

Reproductive Medicine doi: 10.3390/reprodmed5040021

Authors: Anna Gideon Kasililika Hindu Ibrahim Hussein Henry Stephen Joseph Secilia Kapalata Ng’weshemi Alphonce Bilola Chandika

(1) Background: Infertility is a global health problem that affects one of six couples worldwide, leading to significant negative impacts on their quality of life. Despite numerous studies on infertility patterns and sociodemographic characteristics, there remains a lack of clarity on these aspects among patients seeking care in Tanzania. (2) Methods: This hospital-based analytical cross-sectional study aimed to determine infertility patterns and sociodemographic characteristics among 385 randomly selected male and female patients attending the Benjamin Mkapa Hospital. Structured interviews using a clinical proforma collected data on the patterns of infertility and sociodemographic characteristics of the participants. The analysis included descriptive statistics and logistic regression. (3) Results: The findings indicated that the dominant pattern of infertility for both male and female participants was secondary infertility, accounting for 59.00% (228). Multivariate logistic regression analysis for both male and female patients revealed sociodemographic characteristics of infertility: age (38–43) years, AOR 5.068, 95% CI 1.573–16.33, p = 0.007), and duration of cohabiting or marriage of more than 10 years (AOR 0.406,95% CI 0.189–0.873, p = 0.021). (4) Conclusion: Integrating reproductive health education on appropriate fertility age into the reproductive health package and enhancing fertility care in public hospitals in Tanzania is recommended.

Reproductive Medicine doi: 10.3390/reprodmed5040020

Authors: Katherine Doughty Fachon Samantha Truong Sahana Narayan Christina Duzyj Buniak Katherine Vergara Kruczynski Autumn Cohen Patricia Barbosa Amanda Flynn Annekathryn Goodman

Background/Objectives: Disrespectful care of birthing persons during childbirth has been observed as a global issue and a possible factor influencing maternal morbidity and mortality. While birthing persons’ experiences of mistreatment in childbirth have been examined, perceptions from obstetrical providers of respectful maternity care have been understudied. Methods: A mixed-method cross-sectional study was conducted in Boston from April 2023 to January 2024 among 46 labor and delivery physicians, midwives, and nurses at Massachusetts General Hospital. The survey evaluated their observation of disrespectful care, the performance of respectful care, and stress and support factors influencing respectfulness of care. Results: The most reported observed disrespectful behaviors were dismissing patients’ pain (87.0%), discriminatory care based on physical characteristics (67.4%) and race (65.2%), and uncomfortable vaginal examinations (65.2%). Respondents self-reported very high levels of respectful maternity care performance. Reported barriers to respectful care included workload (76.1%) and fatigue (60.9%). Conclusions: Disrespectful care in childbirth is an issue reported by healthcare providers. Implicit bias and the working conditions of health care providers are factors in disrespectful care. This information can be used to strategize future training and other areas of intervention to improve maternity care.

Reproductive Medicine doi: 10.3390/reprodmed5040019

Authors: Kelly Muller Amelie Carballo Karina Vega Becky Talyn

Background/Objectives: As the incidence of autism spectrum disorder (ASD) and use of assisted reproductive technologies (ART) continue to rise in tandem, their relationship to one another, as well as the general risks of ART, are increasingly being explored. The purpose of this review is to summarize the literature on ASD risk, as well as the risks for other neurological and neurodevelopmental disorders, in children born following the implementation of ART. Methods: Here we review studies published between 2000−2023 that elucidate relationships between ASD and some of the most common forms of ART, including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), using fresh vs. frozen embryo transfer. Articles were identified by searching Google Scholar and PubMed databases. Results: Though some studies report adverse neurodevelopmental outcomes in ART-conceived children, such as ASD, attention-deficit/hyperactivity disorder (ADHD), and cerebral palsy, a majority of studies do not show a significant association between ART and neurodevelopmental disorders. Additionally, many confounding factors like multiple and preterm births, underlying infertility, and advanced parental age have been discussed, highlighting the need for studies that effectively control for these confounders. Potential mechanisms implicated in the pathogenesis of ASD, including epigenetic mechanisms of gene expression, that may be related to ART procedures, are also discussed. Conclusion: ART may pose a low additional risk to development of ASD, but confounding factors likely account for most of this risk. Several steps in the process of ART may cause epigenetic changes that are implicated in the development of ASD.

Reproductive Medicine doi: 10.3390/reprodmed5040018

Authors: Cristina Taliento Alba Rondoni Gennaro Scutiero Matteo Pavone Matteo Mordenti Giuseppe Vizzielli Pantaleo Greco

Background: Mullerian duct anomalies include a broad spectrum of genital tract defects that arise from developmental abnormalities of the genital tract. Herlyn–Werner–Wunderlich syndrome (HWWS) refers to the combination of uterus didelphys, blind hemivagina and ipsilateral renal agenesis. In the literature, the syndrome often appears as a few sporadic case reports. Case: We report a case of symptomatic Herlyn–Werner–Wunderlich syndrome diagnosed by transavaginal scan and MRI and successfully treated with a laparoscopic-assisted hysteroscopic vaginal septum resection. The postoperative course was without complications, and clinical symptoms completely resolved the surgery. Summary and Conclusions: Combination of laparoscopy and hysteroscopy was found to be an easy, safe, effective and appropriate approach for patients with HWWS.

Reproductive Medicine doi: 10.3390/reprodmed5040017

Authors: Lindsey A. Roth Elana Kreiger-Benson Steven Friedman Dana R. Gossett Lisa Shanahan

Background: Preterm inductions may be necessary for maternal comorbidities or fetal abnormalities. Previous studies have identified risk factors for undergoing a cesarean delivery (CD). Our study examined the insertion-to-expulsion time (IET) of cervical ripening balloons (CRB) in preterm inductions that achieved vaginal delivery (VD) compared to CD. Methods: This was a retrospective cohort study of preterm inductions with CRB between 2010 and 2021. Primary outcome was IET of CRB. IRB approval was obtained. Results: The study included 82 women. IET for cesarean patients was significantly greater, and required more removal of CRB at the allotted 12 h. Dilation before and after CRB was significantly greater in the vaginal cohort. There was no significant difference in maternal comorbidities, indication for induction or neonatal complications. Conclusions: Maternal comorbidities, induction indication and neonatal complications were similar between cohorts, making trial of induction with CRB in preterm women a reasonable option. Spontaneous expulsion of CRB and greater dilation may be predictors of vaginal delivery.

Reproductive Medicine doi: 10.3390/reprodmed5030016

Authors: Lisa A. McNamee Sharon Amir Kiger Lau

Septic abortion can lead to severe maternal morbidity and mortality. The management of septic abortion can be complicated by a history of radical trachelectomy and transabdominal cerclage placement. A 33-year-old G1P0 at 17 weeks and 6 days gestation presented in severe septic shock after being diagnosed 6 days prior with previable rupture of membranes at an outside hospital and managed expectantly. History was notable for cervical adenocarcinoma status post radical trachelectomy and transabdominal cerclage placement. Due to uterine occlusion from the cerclage, the patient underwent emergent uterine evacuation via an abdominal approach. The risks and benefits of expectant management of pre-viable rupture of membranes in patients with abdominal cerclage should be weighed very cautiously. Among women with abdominal cerclage for whom uterine evacuation is indicated, a transabdominal approach may be necessary.

Reproductive Medicine doi: 10.3390/reprodmed5030015

Authors: Melissa A. Salinas Savita Potarazu Sara Rahman Do H. Lee Lydia Deaton Julia Whitley Devin Hill Kharastin L. Chea-Howard Ciara Bryson Charelle M. Carter-Brooks

Background: Obstetric Anal Sphincter Injuries (OASI) are associated with significant morbidity. Data regarding induction of labor (IOL) and risk of OASI is conflicting. The objective of this study is to evaluate if IOL increases the odds of OASI when compared to spontaneous labor. Methods: This is a retrospective case–control study in women with term, singleton pregnancies, who had a vaginal delivery at a single, academic center in an urban setting from October 2015 to December 2021. Individuals with the primary outcome, OASI, were identified and matched with controls (no OASI) by delivery date. Results: 303 OASI individuals were identified and matched with 1106 controls. Women with OASI were more likely to be White or Asian, have commercial insurance, and have a previous cesarean delivery (CD). IOL increased the likelihood of OASI by 49% compared to spontaneous labor (OR 1.49, 95% CI [1.138, 1.949]). IOL was no longer significant when adjusting for confounding variables and known risk factors. Conclusion: IOL was not associated with OASI when accounting for known antepartum and intrapartum risk factors. Further investigation of modifiable and non-modifiable risks during labor is imperative to decrease the risk of OASI and associated pelvic floor disorders.

Reproductive Medicine doi: 10.3390/reprodmed5030014

Authors: Rebecca M. Adams Bernard Gonik

Maternal vaccination is a safe and effective means of preventing infection in pregnant women, their fetuses, and infants after birth. Several vaccines are routinely administered in pregnancy as a valuable part of prenatal care with supporting recommendations from national and international health organizations. Fears concerning vaccine safety in pregnancy are pervasive despite sufficient available safety data to support their use, leading to underutilization of maternal immunization. Despite this hesitancy, the field of maternal vaccination is evolving to include more vaccines in the routine prenatal vaccination schedule, including the new RSV vaccine. This review discusses the currently recommended vaccines in pregnancy, evidence for their use, and an overview of ongoing clinical trials investigating prospective vaccines for pregnant women.

Reproductive Medicine doi: 10.3390/reprodmed5030013

Authors: Daniela Hristov Done Stojanov

In this study, we analyzed the regulatory properties of 26 (twenty-six) genes associated with nonsyndromic male infertility. We applied an in silico analysis in order to determine the number and distribution of promoters and identify relevant promoter consensus sequences and potential transcription factors. Underlining the concept of alternative transcriptional initiation (ATI), we have found that 65.4% of genes associated with nonsyndromic male infertility have 1 (one) to 6 (six) promoters, located in the region 1 kb upstream of the TSS, and 41% of them are located at a position below −500 bp. Although the TATA box consensus sequence TAWAAA, such as W is A or T, appears at a common location in all genes, it is shifted for at least 10 bp in the EFCAB9 gene. The C2H2 zinc finger is found to be the most significant common transcription factor, binding genes’ promoters GLIS1, ZSCAN21, GLIS3, GLIS1, ZNF770, ZNF780A, ZNF81, and ZNF264. On the other hand, basic leucine zipper factors (bZIPs) bind the JUNB gene promoter specifically, exhibiting unique regulatory properties of all genes associated with nonsyndromic male infertility. Two genes, NANOS1 and ZMYND15, are expected to be less susceptible to DNA methylation, due to the high density of CpG content found in their promoter regions.

Reproductive Medicine doi: 10.3390/reprodmed5030012

Authors: Farzan Vahedifard Xuchu Liu Kranthi K. Marathu H. Asher Ai Mark P. Supanich Mehmet Kocak Seth Adler Shehbaz M. Ansari Melih Akyuz Jubril O. Adepoju Sharon Byrd

Accurately predicting a fetus’s gestational age (GA) is crucial in prenatal care. This study aimed to develop an artificial intelligence (AI) model to predict GA using biometric measurements from fetal brain magnetic resonance imaging (MRI). We assessed the significance of using different reference standards for interpreting GA predictions. Measurements of biparietal diameter (BPD), fronto-occipital diameter (FOD), and head circumference (HC) were obtained from 52 normal fetal MRI cases from Rush University. Both manual and AI-based methods were utilized, and comparisons were made using three reference standards (Garel, Freq, and Bio). The AI model showed a strong correlation with manual measurements, particularly for HC, which exhibited the highest correlation with actual values. Differences between GA predictions and picture archiving and communication system (PACS) records varied by reference, ranging from 0.47 to 2.17 weeks for BPD, 0.46 to 2.26 weeks for FOD, and 0.75 to 1.74 weeks for HC. Pearson correlation coefficients between PACS records and GA predictions exceeded 0.97 across all references. In conclusion, the AI model demonstrated high accuracy in predicting GA from fetal brain MRI measurements. This approach offers improved accuracy and convenience over manual methods, highlighting the potential of AI in enhancing prenatal care through precise GA estimation.

Reproductive Medicine doi: 10.3390/reprodmed5030011

Authors: Katharine R. B. Phillips Alexander G. Kuzma-Hunt Michael S. Neal Connie Lisle Hariharan Sribalachandran Ronald F. Carter Shilpa Amin Megan F. Karnis Mehrnoosh Faghih

Preimplantation genetic testing for aneuploidy (PGT-A) has become a useful approach for embryo selection following IVF and ICSI. However, the biopsy process associated with PGT-A is expensive, prone to errors in embryo ploidy determination, and potentially damaging, impacting competence and implantation potential. Therefore, a less invasive method of PGT-A would be desirable and more cost-effective. Noninvasive methods for PGT-A (ni-PGT-A) have been well-studied but present limitations in terms of cf-DNA origin and diagnostic accuracy. Minimally invasive pre-implantation genetic testing (mi-PGT-A) for frozen-thawed embryo transfer is a promising, less studied approach that utilizes a combination of spent culture media (SCM) and blastocoelic fluid (BF)-derived cell-free (CF)-DNA for genetic testing. This study aimed to optimize the effectiveness of mi-PGT-A for aneuploidy diagnosis by investigating the optimal temporal sequence for this protocol. SCM+BF was collected at either 48 or 72 h of culture after thawing day 3 preimplantation embryos. cf-DNA in the SCM+BF was amplified, analyzed by next-generation sequencing (NGS) and compared with results from the corresponding whole embryos (WEs) obtained from human embryos donated for research. Fifty-three (42 expanded blastocysts, 9 early blastocysts, and 2 morula) WE and SCM+BF samples were analyzed and compared. The overall concordance rate between SCM+BF and WE was 60%. Gender and ploidy concordance improved with extended culture time from 48 h (73% and 45%) to 72 h (100% and 64%), respectively. These results demonstrate that SCM+BF-derived cf-DNA can be successfully used for mi-PGT-A. Our findings indicate that longer embryo culture time prior to SCM+BF-derived cf-DNA analysis improves DNA detection rate and concordance with WEs and decreases the proportion of false positive results.

Reproductive Medicine doi: 10.3390/reprodmed5020010

Authors: Sarah King Florence Osei Courtney Marsh

This study investigates the association between body mass index (BMI) and the composition of the endometrial microbiota in infertile women of childbearing age. This is a retrospective clinical study comparing the endometrial microbiota across body weight in 132 patients presenting for care at an infertility clinic. The reason for infertility was recurrent pregnancy loss (RPL) or implantation failure with a prior IVF cycle. Microbe analysis was completed by Igenomix Laboratory (Valencia, Spain) using two comprehensive panels. Patients were separated into three groups based on their results: normal, dysbiotic, and pathogenic. Prevalence of these groups was compared across BMI categories and statistical analysis was used to determine significance. Of the 132 endometrial samples collected, 80 (60.6%) were normal, 16 (12.1%) were dysbiotic, and 36 (27.3%) were pathogenic. Patients with a BMI ≥ 30 showed a statistically significant increase in pathogenic endometrium compared to normal weight controls (p = 0.029). Our conclusion is that the prevalence of pathogenic endometrium was significantly higher in the obese group compared with normal weight controls. There is a possible association between obesity and the endometrial microbiome.

Reproductive Medicine doi: 10.3390/reprodmed5020009

Authors: Brooke Neumann Nicole Weitz Jerome H. Check Carrie Wilson Ann Diantonio Megan O’Neil

Background: This study’s aim was to determine whether diminished oocyte reserve (DOR) increases the risk of having a fetus with trisomy 13, 18, or 21 at 10 weeks as evaluated by non-invasive prenatal testing (NIPT) and to evaluate the confounding effect of advanced age. Methods: NIPT was undertaken in all pregnancies conceived through natural treatment or assisted reproductive technology that reached 10 weeks from conception with a viable fetus from one infertility center. Data were stratified according to serum anti-Mullerian hormone (AMH) < 1 ng/mL and ≥1 ng/mL. Results: No woman < 39 or with AMH ≥ 1 ng/mL showed trisomy 13, 18, or 21 by NIPT. Only women ≥ age 39 with DOR had one of these trisomies. Conclusions: Hopefully these data, coupled with other factors, e.g., etiology of infertility, age, insurance, or financial circumstances, and personal views of pregnancy termination, will aid patients with DOR when choosing treatment options, including natural conception, IVF-ET, IVF with pre-implantation genetic testing for aneuploidy, or transfer of fertilized donor eggs.

Reproductive Medicine doi: 10.3390/reprodmed5020008

Authors: Yasunari Miyagi Yasuyuki Mio Keitaro Yumoto Rei Hirata Toshihiro Habara Nobuyoshi Hayashi

The retrospective noninterventional study investigated the kinetic energy of video images of 18 fertilized eggs (7 were normal and 11 were abnormal) recorded by a time-lapse device leading up to the beginning of the first cleavage. The norm values of cytoplasmic particles were measured by the optical flow method. Three phase profiles for normal cases were found regarding the kinetic energy: 2.199 × 10−24 ± 2.076 × 10−24, 2.369 × 10−24 ± 1.255 × 10−24, and 1.078 × 10−24 ± 4.720 × 10−25 (J) for phases 1, 2, and 3, respectively. In phase 2, the energies were 2.369 × 10−24 ± 1.255 × 10−24 and 4.694 × 10−24 ± 2.996 × 10−24 (J) (mean ± SD, p = 0.0372), and the time required was 8.114 ± 2.937 and 6.018 ± 5.685 (H) (p = 0.0413) for the normal and abnormal cases, respectively. The kinetic energy change was considered a condition for applying the free energy principle, which states that for any self-organized system to be in equilibrium in its environment, it must minimize its informational free energy. The kinetic energy, while interpreting it in terms of the free energy principle suggesting clinical usefulness, would further our understanding of the phenomenon of fertilized egg development with respect to the birth of human life.

Reproductive Medicine doi: 10.3390/reprodmed5020007

Authors: Taniya V. Walker Ciara Bryson Sara Rahman Charelle M. Carter-Brooks

Introduction and Hypothesis: Obstetric anal sphincter injuries (OASIs) complicate 5.8% of vaginal deliveries. Our objective was to assess if the primary delivery provider, a nurse-midwife versus physician obstetrician, is associated with OASIs. Methods: We performed a secondary analysis of the Consortium of Safe Labor, a multicenter, retrospective cohort study. Included were nulliparous women with singleton, vaginal delivery at ≥37 weeks from 2002 to 2008. Women were excluded if delivery was complicated by shoulder dystocia or from sites without midwife deliveries. Student’s t-tests, chi-squared analysis, and Fisher’s exact test were used as appropriate. Multivariable logistic regression and propensity score-matching analyses were performed. Results: Of 228,668 births at 19 sites, 2735 births from 3 sites met the inclusion criteria: 1551 physician and 1184 midwife births. Of all births, 4.2% (n = 116) were complicated by OASIs. Physician patients were older, more often White, privately insured, with higher BMI, more medical co-morbidities, and labor inductions/augmentations. Midwife patients had higher fetal gestational age and infant birth weights (all p < 0.05). OASIs were more common in physician compared to midwife births (5.9% vs. 2.0%, p < 0.0001). This difference persisted in multivariable logistic regression. OASIs were 2.4 (95%CI 1.5–3.9) times more likely with physician delivery when controlling for maternal heart disease, episiotomy, increasing maternal age, decreasing maternal BMI, non-White race, and increasing birthweight. The AUC was 0.78. With propensity score matching, OASI rates remained higher amongst physician births (6.6% vs. 1.8%, p < 0.0001; aOR 3.8 (95%CI 2.0–7.1)). Conclusion: OASIs were more common in physician compared to midwife deliveries even when controlling for other associated factors.

Reproductive Medicine doi: 10.3390/reprodmed5020006

Authors: Susumu Tanaka Misa Sawachika Namika Yoshida Kensuke Futani Hiromi Murata Hidetaka Okada

Interleukin (IL) 17A has been implicated in preeclampsia, preterm labor, and miscarriage. IL17A production in non-lymphoid tissues is mainly carried out by unconventional γδ17T cells. Innate lymphoid cells (ILCs) 3, a subgroup of innate lymphocytes, can also be a source of IL17A in the endometrium and are required from implantation to early pregnancy, with their regulation ensuring that pregnancy continues. Herein, we examined the expression of γδ17T cells and ILC3 regulators IL1B, IL23A, and IL17D and IL17A receptors (IL17RA/IL17RC) in human endometrial stromal cells (EnSCs) and cell lines (KC02-44D). Accordingly, quantitative polymerase chain reaction and immunoblotting were employed. IL1B, IL23A, and IL17D were significantly upregulated in decidualized EnSCs and KC02-44D cells. A significant augmentation in IL17RA/IL17RC was also observed in decidualization. IL17A stimulation of KC02-44D cells during decidualization suppressed the decidualization marker IGFBP1. The involvement of transcription factor Forkhead box protein O1 (FOXO1) in this repression was reflected by its translocation from the nucleus into the cytoplasm. A role for IkB kinase alpha in FOXO1 phosphorylation-mediated migration was also suggested. Taken together, our findings indicate that the secretion of IL17A by γδ17T and ILC3 cells in the uterus contributes to EnSCs function and may play critical roles in regulating IGFBP1-mediated implantation and fetal growth.

Reproductive Medicine doi: 10.3390/reprodmed5020005

Authors: Lindsay A. Hartup Elizabeth Guarisco Xuemei Song Zhu Wang Angela R. Boyd

There are established reference ranges for many laboratory values during pregnancy. Fewer studies exist regarding the expected white blood cell (WBC) count after delivery. The aim of this study was to determine appropriate postpartum leukocytosis in a diverse patient cohort. Patients who delivered a live fetus at 37 weeks or later were retrospectively identified. Complete blood counts collected on hospital admission and postpartum day one were used to quantify the change in WBC count associated with delivery. A total of 2245 patients were included; of these patients, 1476 delivered vaginally and 769 delivered via cesarean section. The average change in WBC count was 2.99 × 103/mm3. A WBC count of 20.19 × 103/mm3 defined the 95th percentile. The average rise in WBC count was 3.31 × 103/mm3 after vaginal delivery and 2.34 × 103/mm3 after cesarean section (p < 0.001). Patients with chorioamnionitis or endometritis had an average postpartum WBC rise of 7.38 × 103/mm3 compared to 2.99 × 103/mm3 in controls (p < 0.001). There was no difference in WBC count rise with comorbid asthma, diabetes, or chronic hypertension. A greater WBC count rise was found in patients with pregnancy-induced hypertension. This study provides reference values for the average rise in WBC count after delivery and the 95th percentile postpartum WBC count in a diverse, medically complex patient population with and without delivery complications. Our findings further highlight maternal medical comorbidities that may contribute to the degree of postpartum leukocytosis.

Reproductive Medicine doi: 10.3390/reprodmed5020004

Authors: Bruce I. Rose Kevin Nguyen Samuel E. Brown

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Reproductive Medicine doi: 10.3390/reprodmed5010003

Authors: Nadi Nina Kaonga Yanghee Courbron Emmy Holmgren Eliot Konzal Whitney Williams Mary Brandes Caroline Foust-Wright

Background: Higher levels of pre-operative anxiety are associated with adverse outcomes according to the cardiothoracic and orthopedic literature on emergent surgeries. There are limited data on pre-operative anxiety levels in the gynecologic setting. This study sought to identify predictive variables for high pre-operative anxiety levels in patients undergoing major urogynecologic surgery. Methods: Pre- and post-operative surveys that included demographic data, a modification of the Amsterdam Pre-Operative Anxiety and Information Scale, and open-ended questions regarding anxiety were administered. Descriptive, univariate and multivariate analyses were used to analyze the quantitative elements of the survey data. The qualitative components of the survey data were coded and analyzed using thematic analyses. Results: A total of 54 participants completed the pre-operative survey. The median age was 62 years old, and the majority were employed (n = 34, 60.7%). Roughly 1/3 had been diagnosed with a mental health condition (n = 19, 33.9%) and nearly all had other health conditions (n = 51, 91%). The baseline APAIS score ranged from 9 to 40, with higher scores reflecting higher levels of pre-operative anxiety. The median APAIS score was 24, with a score equal to or greater than 30 being in the highest tertile. Conclusion: No associations were made between the variables and pre-operative anxiety levels. However, useful insights into our patient population were made.

Reproductive Medicine doi: 10.3390/reprodmed5010002

Authors: Sara Yalda Ghaur Pernille Bundgaard Grinderslev Magnus Leth-Møller Per Glud Ovesen Jens Fuglsang Sanne Fisker H. David McIntyre Ulla Kampmann

Pregnancies complicated by type 1 diabetes (TID) are associated with an increased risk of obstetric and neonatal adverse outcomes. Optimal glycemic control prior to and through pregnancy is crucial to reduce complications. The use of diabetes technology is rapidly increasing. The aim of the study was to investigate the use and effects of diabetes technology in pregnant women with type 1 diabetes. A retrospective cohort study was conducted; 84 women were included in the analysis and were divided into subgroups according to their glucose monitoring method and insulin delivery method. HbA1c values declined during pregnancy in all subgroups with no significant difference between the subgroups. A difference was, however, found in birth weight z-scores. Women using a sensor and an insulin pump had larger babies compared to women without these treatment modalities. The results of the study indicate that diabetes technology, including insulin pumps and/or glucose sensors are not superior to self-monitoring blood glucose measurement and multiple daily injection insulin therapy, which is comforting in the light of the unequal access to health benefits.

Reproductive Medicine doi: 10.3390/reprodmed5010001

Authors: Katrina L. Curtis Kelsey M. Hirshi Kary Tsai Evan T. Clark Brendan M. Stapley Benjamin T. Bikman Paul R. Reynolds Juan Arroyo

Exposure to secondhand smoke (SHS) during fetal development results in negative postnatal effects, including altered organ development, changes in metabolism, and increased risk of respiratory illness. Previously, we found the induction of intrauterine growth restriction (IUGR) dependent on the expression of the receptor for advanced glycation end-products (RAGE) in mice treated with SHS. Furthermore, antenatal SHS exposure increases RAGE expression in the fetal lung. Our objective was to determine the postnatal effects of antenatal SHS treatment in 4- and 12-week-old offspring. Pregnant animals were treated with SHS via a nose-only delivery system (Scireq Scientific, Montreal, Canada) for 4 days (embryonic day 14.5 through 18.5), and offspring were evaluated at 4 or 12 weeks of age. Animal and organ weights were measured, and lungs were histologically characterized. Blood pressure and heart rates were obtained, and RAGE protein expression was determined in the lungs of control and treated animals. We observed the following: (1) significant decreases in animal, liver, and heart weights at 4 weeks of age; (2) increased blood pressure in 4-week-old animals; and (3) increased RAGE expression in the lungs of the 4-week-old animals. Our results suggest an improvement in these metrics by 12 weeks postnatally such that measures were not different regardless of RA or SHS exposure. Increased RAGE expression in lungs from 4-week-old mice antenatally treated with SHS suggests a possible role for this important smoke-mediated receptor in establishing adult disease following IUGR pregnancies.

Reproductive Medicine doi: 10.3390/reprodmed4040023

Authors: Meghan C. H. Ozcan Julienne Chaqour Morgan F. Woodman-Sousa Kathryn J. Grive

Current safety data on chemotherapy during pregnancy are based on studies which focus on the mother and do not explore reproductive health and fecundity potential within the exposed offspring. We designed this randomized ex vivo animal study to evaluate the effect of chemotherapy on the developing ovarian reserve in the exposed offspring. Specimens (100 postnatal day zero C57BL/6 mouse ovaries) were randomized to control or chemotherapy drug exposure and maintained in a hanging well organ culture. Murine ovarian reserve establishment mirrors activity seen in the human fetus but with a significant time shift of the transition to meiotic arrest to the postnatal period. Exposures included: doxorubicin, cyclophosphamide, paclitaxel, docetaxel, and cisplatin. Doxorubicin resulted in a significant loss of 95.2% (p < 0.0001) of oocyte density compared to controls. Cyclophosphamide also caused depletion of 50.5% (p < 0.0001) of oocyte density. Cisplatin, docetaxel, and paclitaxel all demonstrated unique phenotypical changes on the ovaries and their oocytes, without a significant decrease in oocyte density over a five-day exposure. Exposure to chemotherapy may result in profound loss of oogonia during the transition to mature oocytes.

Reproductive Medicine doi: 10.3390/reprodmed4040022

Authors: Stephanie C. Laniewski LauraAnne Hirschler Anwar M. Iqbal Neil S. Seligman

This case presents a novel occurrence of a de novo BRCA1 gene deletion in a fetus with a cystic hygroma. Chorionic villus sampling (CVS) was performed for chromosome G-banding analysis, demonstrating a normal karyotype: 46, XX. Chromosome microarray analysis performed as a reflex test revealed an 80 kb deletion on 17q21.31, encompassing the BRCA1 gene. Follow-up FISH analysis performed on parental blood samples yielded negative results, confirming that the deletion was de novo in the fetus. Subsequent anatomic ultrasound evaluation showed no identifiable structural defects, and it was concluded that the microdeletion was unlikely to be the cause of the cystic hygroma. Regardless, it will be imperative that the patient’s daughter be appropriately counseled regarding the implications of carrying a BRCA1 deletion and the need for heightened surveillance in adulthood. As BRCA1 genetic testing is traditionally performed on adult patients with informed consent, this case report highlights the need for ongoing conversations and research in the management of incidental fetal diagnosis discovered during routine prenatal testing, as well as the care and counseling of these patients and their families.