Reproductive Medicine

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

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

Background: Transposition of the great arteries (TGA) is a common critical neonatal congenital heart defect. After birth, physiological shunts close rapidly, necessitating early treatment with prostaglandin infusion and balloon-atrial septostomy. Timing of delivery is challenging, balancing the risks and advantages of early-term delivery and specialized care. The aim of this study is to assess the safety of a full-term delivery policy in fetuses diagnosed with TGA. Methods: A retrospective chart review was conducted of 17 women with a prenatal diagnosis of fetal TGA at Virgen del Rocío University Hospital between 2015 and 2021. Primary outcomes included: incidence of preterm, early-term, full-term, and late-term delivery, and rate of cesarean section. Secondary outcomes included: Saturday to Sunday admission and birth, and delivery between 0:00 a.m. and 8:00 a.m. Results: Full-term birth was achieved in 94.1%, reaching a low cesarean delivery rate (17.6%). A total of 82.4% of infants were born on weekdays, and only in three of the cases (17.6%) did delivery occur between 0 a.m. and 8 a.m. The median birth weight was 3300 g. Intravenous prostaglandins were administered in all cases, and 94.1% required balloon-atrial septostomy. Conclusions: In our study favoring full-term delivery, we reduce early-term deliveries and the cesarean section rate in prenatally diagnosed TGA. Full article

Recent developments in stem cell technologies have made significant advancements in the field of in vitro gametogenesis. In vitro gametogenesis (IVG) is a promising technology where functional gametes (sperm or egg cells) can be generated from stem cells. Scientists have made continuous advancements in the field and successfully derived fully functional sperm from stem cells in mice. Two recent papers generated excitement in IVG by generating bi-maternal and bi-paternal mice from embryonic stem cells (ESCs) and pluripotent stem cells (PSCs). IVG is a promising technology with potential applications that include infertility treatment, fertility preservation, same-sex reproduction, bypassing oocyte depletion in women with advanced age, conservation biology, genetic disorder prevention, and research into human germ cell development. In vitro spermatogenesis (IVS) is the attempt to recreate the process of spermatogenesis in a culture system. Spermatogenesis is essential for male fertility and reproductive health, but it can be impaired by various factors such as genetic defects, environmental toxicants, infections, aging, or medical therapies. Spermatogenesis is a complex and highly regulated process involving multiple cell proliferation, differentiation, and maturation stages. The main challenges of IVS are to provide a suitable microenvironment that mimics the testis in vivo, to support the survival and development of all the cell types involved in spermatogenesis, and to achieve complete and functional spermatogenesis. Therefore, there is a great interest in developing methods to study spermatogenesis in vitro, both for basic research and clinical applications. This review covers recent developments in in vitro spermatogenesis in the past two years. Advances in tissue engineering and regenerative medicine have introduced techniques like ex vivo tissue culture and technologies such as bioreactors, microfluidic systems, and organoids. Bioreactors and microfluidic systems replicate physiological conditions for tissue and cell cultivation, while organoids model organ functionality. Meanwhile, scaffolds, made from various materials, provide essential structural support, guiding the growth and organization of cells into functional tissues. Full article