Reproductive Medicine

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

(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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article