Reprod. Med., Volume 4, Issue 1 (March 2023) – 8 articles

Purpose: In vitro maturation (IVM) continues its evolution as new ideas are introduced with the objective of making the IVM procedure easier and more effective. This study combines ideas believed likely to improve the IVM outcome or make the IVM oocyte identification process easier. Methods: A cohort of 45 women underwent an IVM cycle in which letrozole was used with the theoretical objective of improving the competence of small antral follicles, the oocyte aspiration technique was modified to minimize the time between oocyte aspiration and oocyte identification, and blastocysts were transferred during a subsequent cycle with controlled endometrial development. Results: Measures of oocyte competence used for these prospectively followed cycles were as follows: the maturation rate was 90.5%, the fertilization rate was 92.4%, the cleavage rate was 94.6%, the usable blastulation rate per zygote was 50.2%, and the implantation rate was 34.2%. Per transfer, the biochemical pregnancy rate was 63.2%, the clinical pregnancy rate was 55.3% and the ongoing/delivered pregnancy rate at the end of the first trimester was 47.4%. The miscarriage rate for clinical pregnancies in the first trimester was 14.3% and the ongoing twinning rate was 11.1%. Full article

Polycystic ovary syndrome is a common endocrine disorder affecting 5–20% of women in association with metabolic disorders and insulin resistance. Patients with PCOS are also at increased risk of developing cardiovascular sound aspects of polycystic ovaries and metabolic complications, a psychosocial impact that exists, which is poorly known, assessed and treated. The delay, sometimes long, for diagnosis and its announcement has a strong impact on the feelings and life projects of these patients. Psychological co-morbidities such as depression, anxiety, eating disorders as well as a decrease in self-esteem and quality of life are frequently described in these patients and must, therefore, be screened and treated. Full article

Background: Single cell transcriptomics offers an avenue for predicting, with improved accuracy, the gene networks that are involved in the establishment of the first direct cell–cell interactions between the blastocyst and the maternal luminal epithelium. We hypothesised that in silico modelling of the maternal–embryonic interface may provide a causal model of these interactions, leading to the identification of genes associated with a successful initiation of implantation. Methods: Bulk and single cell RNA-sequencing of endometrial epithelium and scRNAseq of day 6 and 7 trophectoderm (TE) were used to model the initial encounter between the blastocyst and the maternal uterine lining epithelium in silico. In silico modelling of the maternal–embryonic interface was performed using hypernetwork (HN) analysis of genes mediating endometrial–TE interactions and the wider endometrial epithelial transcriptome. A hypernetwork analysis identifies genes that co-ordinate the expression of many other genes to derive a higher order interaction likely to be causally linked to the function. Potential interactions of TE with non-ciliated luminal cells, ciliated cells, and glandular cells were examined. Results: Prominent epithelial activities include secretion, endocytosis, ion transport, adhesion, and immune modulation. Three highly correlated clusters of 25, 22 and 26 TE-interacting epithelial surface genes were identified, each with distinct properties. Genes in both ciliated and non-ciliated luminal epithelial cells and glandular cells exhibit significant functional associations. Ciliated cells are predicted to bind to TE via galectin–glycan interaction. Day 6 and day 7 embryonic–epithelial interactomes are largely similar. The removal of aneuploid TE-derived mRNA invoked only subtle differences. No direct interaction with the maternal gland epithelial cell surface is predicted. These functional differences validate the in silico segregation of phenotypes. Single cell analysis of the epithelium revealed significant change with the cycle phase, but differences in the cell phenotype between individual donors were also present. Conclusions: A hypernetwork analysis can identify epithelial gene clusters that show correlated change during the menstrual cycle and can be interfaced with TE genes to predict pathways and processes occurring during the initiation of embryo–epithelial interaction in the mid-secretory phase. The data are on a scale that is realistic for functional dissection using current ex vivo human implantation models. A focus on luminal epithelial cells may allow a resolution to the current bottleneck of endometrial receptivity testing based on tissue lysates, which is confounded by noise from multiple diverse cell populations. Full article

Single embryo transfer (SET) is a technique used in assisted reproductive treatment (ART) that is used to promote singleton pregnancies. To date, there are five reported cases of dizygotic twin pregnancies with mothers who underwent SET. Here, we present a sixth case of a dichorionic, diamniotic twin pregnancy with sex discordance. The patient is a 34-year-old woman with unexplained secondary infertility who underwent in vitro fertilization (IVF) and frozen-thawed embryo transfer from a SET. The ultrasonographic images from the first and second trimester scans identified dichorionic, diamniotic twin gestations. The delivery was full term and postnatal genetic testing confirmed 46, XX, and 46, XY offspring. Pathology reports of the placental and membrane findings reported diamniotic, dichorionic twins. There was no zygosity testing conducted, thus it is unknown if the twins are monozygotic or dizygotic. Two possible etiologies for sex-discordant twins, in this case, are concurrent natural conception via breakthrough ovulation at the time of SET, or discordant postzygotic nondisjunction of a single embryo. Multiple gestations may still occur in the setting of SET and zygosity testing in these instances would better elucidate our understanding of this occurrence. Moreover, improved data on the zygosity of multiple gestations following SET may enhance patient counseling. Full article

Maternal marital status, educational levels, and income levels were associated with adverse pregnancy outcomes and placental inflammatory changes, preterm delivery, and stillbirth. We aimed to examine the association of marital status with maternal and neonatal complications and placental pathology in singleton pregnancy. A total of 3724 singleton placentas with maternal neonatal and placental pathology data were included in the study, and there were statistically significant associations between marital status and maternal age, race/ethnicity, maternal BMI at delivery, neonatal birth weight, preeclampsia, and preterm delivery. There were significant associations between marital status and maternal inflammatory response, maternal vascular malperfusion, and meconium stain of fetal membranes. These data demonstrated that marital status affects not only the maternal well-being during pregnancy, but also neonatal birth data and placental pathology. Full article

The aim of the present study was to evaluate the effect of activin A on the activation of in vitro folliculogenesis of human ovarian tissues from transgender men with or without our new compartmented chitosan hydrogel microbioreactor (“three-dimensional (3D)-structure”) enabling a three-dimensional tissue culture. Five fresh ovarian human tissues were cultured in vitro for 20 or 22 days in four groups with 100 ng/mL activin A or without activin A during the last six to eight days of culture, and within a 3D-structure or without the 3D-structure in standard conditions. Follicular density and quality were evaluated, and follicular diameters were measured. Estradiol secretion was quantified. Proliferation and apoptosis through immunostaining were also performed. The proportion of primordial follicles was significantly reduced, and the proportion of primary and secondary follicles was significantly increased in all four groups (p < 0.001). Tertiary follicles were observed in the four culture groups. Activin A supplementation did not significantly affect the follicular density, follicular quality, follicular growth, or estradiol secretion (p > 0.05). The 3D-structure increased the density of primary follicles and decreased the estradiol secretion (p < 0.001). Follicular proliferation was significantly lower in the 3D-structure group compared to the non-3D-structure group (p = 0.008). Regarding follicular apoptosis, it was significantly higher in the activin group compared to the non-activin group (p = 0.006). Activin A did not seem to play a key role in the in vitro folliculogenesis activation in our culture conditions. However, the results may indicate that the 3D-structure could be more physiological and could prevent a detrimental in vitro folliculogenesis flare-up. Full article

The purpose of this project was to evaluate whether screening positive on obstructive sleep apnea questionnaires in the first trimester of pregnancy was associated with miscarriage. This was a secondary analysis of a prospective observational cohort study of participants who were screened for sleep apnea during pregnancy with the Epworth Sleepiness Scale, Berlin Questionnaire, and novel items related to sleep and napping. This secondary analysis was IRB exempt. Our primary outcome was miscarriage in the index pregnancy. An association between responses to the sleep apnea screening questions with miscarriage of the index pregnancy was queried via Poisson regression. We found that gravidae who had elevated scores on both the Epworth Sleepiness Scale and the Berlin Questionnaire were more likely to experience miscarriage than those who had elevated scores on only one questionnaire or neither (p = 0.018). Gravidae who reported snoring (p = 0.042) or hypertension (p = 0.013) in the first trimester were more likely to experience miscarriage than gravidae who did not. Gravidae who reported napping in the first trimester were less likely to experience miscarriage (p = 0.045), even after adjusting for confounding variables (p = 0.007). In conclusion, we found that screening positive on both the Berlin Questionnaire and Epworth Sleepiness Scale was statistically significantly associated with miscarriage prior to adjustment for confounding variables, as did snoring and hypertension. After adjusting for confounding variables, only not napping was associated with miscarriage. Given the small sample size, further investigation into this topic is warranted. Full article