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Review
The Management of Inflammatory Bowel Disease during Reproductive Years: An Updated Narrative Review
Reprod. Med. 2023, 4(3), 180-197; https://doi.org/10.3390/reprodmed4030017 - 03 Aug 2023
Viewed by 295
Abstract
Inflammatory bowel disease (IBD) frequently affects women of childbearing age and often coincides with pregnancy. With an increased incidence of IBD, gastroenterologists and obstetricians are more frequently involved in caring for women of reproductive age. While the development of novel therapies has allowed [...] Read more.
Inflammatory bowel disease (IBD) frequently affects women of childbearing age and often coincides with pregnancy. With an increased incidence of IBD, gastroenterologists and obstetricians are more frequently involved in caring for women of reproductive age. While the development of novel therapies has allowed for successful conception and pregnancy outcomes, many patients may hesitate to conceive due to concerns for presumed adverse IBD effects on maternal and fetal health. As such, a noticeable percentage of patients may choose voluntary childlessness. Indeed, active IBD carries a greater risk of adverse pregnancy outcomes, including a loss of pregnancy, preterm delivery, and emergent C-sections. However, those with a quiescent disease tend to have fewer pregnancy complications. Therefore, it is essential to achieve remission prior to conception to optimize pregnancy outcomes. Dedicated IBD and pregnancy clinics can greatly assist in improving patient knowledge and attitudes towards pregnancy; through individualized pre-conception counseling, education, and medication adherence, the risks of poor pregnancy outcomes can be minimized. Furthermore, it is important for healthcare providers to have a sufficient understanding of the medication safety and tools to measure the disease activity, while counseling patients during gestation and breastfeeding periods. This review article aims to provide the most recent evidence-based management methods for IBD during pregnancy. Full article
(This article belongs to the Special Issue Reviews on Reproductive Biology and Medicine)
Article
Travel during Pregnancy: A Web-Based Survey of People Who Have Been Pregnant within the Past 10 Years
Reprod. Med. 2023, 4(3), 166-179; https://doi.org/10.3390/reprodmed4030016 - 28 Jul 2023
Viewed by 256
Abstract
Travel is frequent among many populations, including pregnant people. The focus of this online survey was to better understand the travel practices of people who have been pregnant within the last ten years. An online survey was conducted for three months through social [...] Read more.
Travel is frequent among many populations, including pregnant people. The focus of this online survey was to better understand the travel practices of people who have been pregnant within the last ten years. An online survey was conducted for three months through social media posts on Facebook and Twitter. Previously pregnant people were asked questions about where they traveled, if they cancelled any travel plans, and travel-related discussions with their obstetric provider. During the three months the survey was open, 469 participants completed the survey. A total of 390 (83.2%) participants traveled domestically, while 114 (24.3%) traveled internationally or between non-contiguous states within the United States of America (USA). Of these respondents, 170 (44.2%) of the domestic travelers and 69 (61.1%) of the international travelers reported discussing travel plans with their OB provider. Additionally, 49 (10.5%) participants cancelled at least one domestic trip and 30 (6.41%) cancelled at least one international trip. Regarding travel discussions, 6 (3.6%) participants who traveled domestically and 2 (2.9%) who traveled internationally reported that their OB provider initiated the conversation. Many pregnant people choose to travel domestically and internationally. However, it is also clear that not all travelers discuss plans with their OB provider, and in few cases does the provider initiate the conversation. Given the frequency with which people travel, pregnant people and their OB providers should have conversations regarding travel to minimize potential risks. Full article
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Review
The Duration of Menstrual Blood Loss: Historical to Current Understanding
Reprod. Med. 2023, 4(3), 145-165; https://doi.org/10.3390/reprodmed4030015 - 26 Jul 2023
Viewed by 336
Abstract
Most published research focuses on the amount of menstrual blood loss and, to a lesser extent, on cyclicity. Little attention has been paid to the duration of bleeding, the factors that enable its cessation within a ‘normal’ timeframe, or to patterns that entail [...] Read more.
Most published research focuses on the amount of menstrual blood loss and, to a lesser extent, on cyclicity. Little attention has been paid to the duration of bleeding, the factors that enable its cessation within a ‘normal’ timeframe, or to patterns that entail interruption and resumption of blood loss. The definition of what constitutes normal remains arbitrary and there is no therapy specifically designed to shorten the duration of bleeding. Here, we critically review the literature that addresses the duration of bleeding and the factors that trigger endometrial breakdown and repair. Available reports used population averages which mask inter- and intra-individual variations. The duration of bleeding is not necessarily linked to the amount of loss but may be influenced by age, ethnicity, habitus, region and altitude of residence, dieting and stress. The onset of bleeding has been linked to declining steroid production by the corpus luteum. There remains considerable controversy around the extent of endometrial shedding at menstruation. This is likely to vary within and between women. The significance of a change from previous patterns, very short or prolonged bleeding, days of light loss or spotting before or after days of bleeding, or of bleed-free days that punctuate flow, remain poorly understood. Full article
Article
Predicting the Need for Insulin Treatment: A Risk-Based Approach to the Management of Women with Gestational Diabetes Mellitus
Reprod. Med. 2023, 4(3), 133-144; https://doi.org/10.3390/reprodmed4030014 - 10 Jul 2023
Viewed by 234
Abstract
Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes including large for gestational age infants. Individualizing the management of women with GDM based on the likelihood of needing insulin may improve pregnancy outcomes. The aim of this study is to identify characteristics [...] Read more.
Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes including large for gestational age infants. Individualizing the management of women with GDM based on the likelihood of needing insulin may improve pregnancy outcomes. The aim of this study is to identify characteristics associated with a need for insulin in women with GDM, and to develop a predictive model for insulin requirement. A historical cohort study was conducted among all women with GDM in a singleton pregnancy at Aarhus University Hospital from 2012 to 2017. Variables associated with insulin treatment were identified through multivariable logistic regression. The variables were dichotomized and included in a point scoring system aiming to predict the likelihood of needing insulin. Seven variables were associated with needing insulin: family history of diabetes, current smoker, multiparity, prepregnancy body mass index, gestational age at the oral glucose tolerance test (OGTT), 2-h glucose value at the OGTT and hemoglobin A1c at diagnosis. A risk score was calculated assigning one point to each variable. On ROC analysis, a cut-off value of ≥3 points optimally predicted a requirement for insulin. This prediction model may be clinically useful to predict requirement for insulin treatment after further validation. Full article
(This article belongs to the Special Issue Recent Advances in Pregnancy-Related Complications)
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Review
Hypo-Osmotic Swelling Test and Male Factor
Reprod. Med. 2023, 4(2), 118-132; https://doi.org/10.3390/reprodmed4020013 - 12 Jun 2023
Viewed by 632
Abstract
For over 30 years, defects of the functional integrity of the sperm membrane, as evidenced by a low hypo-osmotic swelling test when evaluating the semen analysis, are not only associated with male infertility (even with sperm that otherwise seem normal), but unless corrected, [...] Read more.
For over 30 years, defects of the functional integrity of the sperm membrane, as evidenced by a low hypo-osmotic swelling test when evaluating the semen analysis, are not only associated with male infertility (even with sperm that otherwise seem normal), but unless corrected, successful intrauterine pregnancies will rarely ensue. This defect, interestingly, does not impair fertilization of the oocyte, but instead, prevents a normal-appearing embryo from successfully implanting. The frequency in infertile couples increases with advancing age of the male, ranging from 5% in younger males to 25% in men in their late forties or early fifties. It seems to be related to a toxic protein added to the sperm as they traverse the ejaculatory ducts. The defect is very correctable, either by treating the sperm with the protein digestive enzyme chymotrypsin prior to intrauterine insemination and avoidance of unprotected sex prior to ovulation, or in vitro fertilization with intracytoplasmic sperm injection. Unfortunately, this very inexpensive, easy-to-perform test is rarely performed by the large majority of physicians treating infertility. The purpose of this manuscript is to hopefully rekindle interest within the infertility community to add this test to the standard semen analysis. Full article
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Article
A Machine Learning Algorithm Predicting Infant Psychomotor Developmental Delay Using Medical and Social Determinants
Reprod. Med. 2023, 4(2), 106-117; https://doi.org/10.3390/reprodmed4020012 - 05 Jun 2023
Viewed by 379
Abstract
Psychomotor developmental delay in infants includes failure to acquire abilities such as sitting, walking, grasping objects and communication at the ages when most infants have acquired these abilities. Known risk factors include a large number of aspects of family environment, socioeconomic position, problems [...] Read more.
Psychomotor developmental delay in infants includes failure to acquire abilities such as sitting, walking, grasping objects and communication at the ages when most infants have acquired these abilities. Known risk factors include a large number of aspects of family environment, socioeconomic position, problems in pregnancy and birth and maternal health. It is clinically useful to be able to screen for developmental delay so that healthcare interventions can be considered. The present research used machine learning (random forest) to create an algorithm predicting psychomotor delay in 9-month-old infants using information ascertainable at birth and in early infancy. The dataset was the UK longitudinal Millennium Cohort study. In total, 53 predictors measuring socioeconomic indicators, paternal, family and social support for the mother, beliefs about good parenting, maternal health, pregnancy and birth were included in the initial algorithm. Feature reduction showed that of the 53 variables, birthweight, gestational age at birth, pre-pregnancy BMI, family income and parents’ ages had the highest feature importance scores and could alone correctly predict developmental delay with over 99% sensitivity and 100% specificity. No features measuring aspects of early infant care or environment meaningfully added to algorithm performance. The relationships between delay and some of the predictors, particularly income, were nonlinear and complex. The results suggest that the risk of psychomotor developmental delay can be identified in early infancy using machine learning, and that the best predictors are factors present prior to and at birth. Full article
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Opinion
Should Endometriosis-Associated Ovarian Cancer Alter the Management of Women with an Intact Endometrioma in the Reproductive Age?
Reprod. Med. 2023, 4(2), 100-105; https://doi.org/10.3390/reprodmed4020011 - 24 May 2023
Viewed by 788
Abstract
Endometriosis-associated ovarian cancer (EAOC) is an evolving clinical entity believed to develop from ovarian endometriosis. Continuous efforts are nowadays invested in exploring its pathogenesis and causality. Since endometrioma is a widespread sub-type of the disease, malignant transformation to EAOC during reproductive age may [...] Read more.
Endometriosis-associated ovarian cancer (EAOC) is an evolving clinical entity believed to develop from ovarian endometriosis. Continuous efforts are nowadays invested in exploring its pathogenesis and causality. Since endometrioma is a widespread sub-type of the disease, malignant transformation to EAOC during reproductive age may cause much concern and affect its management. The summary relative risk of developing EAOC in women with endometriosis is 1.93-fold compared to women without endometriosis, but its lifetime risk is relatively low, equivalent to 2.1%. EAOC is an age-dependent disease with a mean age of 51.64 ± 3.24 years at diagnosis; 30.68% of patients are below 50, presumably premenopausal. Only 2.10% and 0.017% of cases are below 45 and 40 years, apparently in reproductive age. The evidence is reassuring and implies that managing an intact endometrioma should not be altered in most women of reproductive age. Particular attention should be focused on sporadic cases with an enlarging endometrioma, atypical findings on transvaginal ultrasound (TVUS), and characteristic magnetic resonance imaging (MRI) features. Full article
Article
Infertility Treatment and Hypertension in Pregnancy: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study
Reprod. Med. 2023, 4(2), 89-99; https://doi.org/10.3390/reprodmed4020010 - 18 Apr 2023
Viewed by 893
Abstract
Infertility treatment is a possible factor in hypertensive disorders of pregnancy (HDP). Identifying the characteristics of pregnant women who have undergone infertility treatment and have a potential risk for HDP is valuable for its prevention and treatment. Using data from 12,456 pregnant Japanese [...] Read more.
Infertility treatment is a possible factor in hypertensive disorders of pregnancy (HDP). Identifying the characteristics of pregnant women who have undergone infertility treatment and have a potential risk for HDP is valuable for its prevention and treatment. Using data from 12,456 pregnant Japanese women from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, the association between infertility treatment and HDP was analyzed. A multiple logistic regression model showed an association between infertility treatment and HDP (odds ratio, 1.34; 95% confidence interval, 1.05–1.72). In vitro fertilization/intracytoplasmic sperm injection were also associated with HDP. Moreover, these associations were observed even among women who were not overweight and did not smoke. The application of infertility treatment should be carefully considered, even among women with low modifiable risk factors. Full article
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Review
Genomic Insults and their Redressal in the Eutopic Endometrium of Women with Endometriosis
Reprod. Med. 2023, 4(2), 74-88; https://doi.org/10.3390/reprodmed4020009 - 15 Apr 2023
Viewed by 1013
Abstract
Endometrium, a highly dynamic tissue, is known for its remarkable ability to regenerate, differentiate, and degenerate in a non-conception cycle and transform into a specialized tissue to nurture and protect the embryo in a conception cycle. This plasticity of the endometrium endows the [...] Read more.
Endometrium, a highly dynamic tissue, is known for its remarkable ability to regenerate, differentiate, and degenerate in a non-conception cycle and transform into a specialized tissue to nurture and protect the embryo in a conception cycle. This plasticity of the endometrium endows the uterus to execute its major function, i.e., embryo implantation. However, this boon becomes a bane, when endometrium- or endometrium-like cells adhere, grow, and invade extrauterine sites, leading to endometriosis. Endometrial deposits at the extrauterine site lead to severe pelvic pain, painful menstruation, and infertility in endometriosis. Although benign, endometriotic lesions share several traits with cancerous cells, excessive proliferation, adhesion, invasion, and angiogenesis make endometriotic lesions analogous to cancer cells in certain aspects. There exists evidence to support that, akin to the cancer cell, endometriotic lesions harbor somatic mutations. These lesions are known to experience higher proliferative stress, oxidative stress, and inflammation, which may contribute to somatic mutations. However, it would be of more interest to establish whether in the eutopic endometriosis also, the mutational burden is higher or whether the DNA Damage Response (DDR) is compromised in the eutopic endometrium, in endometriosis. Such investigations may provide more insights into the pathobiology of endometriosis and may also unravel cellular events associated with the origin of the disease. This review compiles inferences from the studies conducted to assess DNA damage and DDR in endometriosis. Full article
(This article belongs to the Special Issue Endometrial Physiology and Pregnancy Success)
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Article
The Effect of In Vitro Maturation (IVM) Protocol Changes on Measures of Oocyte/Embryo Competence
Reprod. Med. 2023, 4(1), 65-73; https://doi.org/10.3390/reprodmed4010008 - 10 Mar 2023
Viewed by 878
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue PCOS and Fertility)
Commentary
The Psychosocial Impact of Polycystic Ovary Syndrome
Reprod. Med. 2023, 4(1), 57-64; https://doi.org/10.3390/reprodmed4010007 - 06 Mar 2023
Viewed by 1379
Abstract
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 [...] Read more.
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
Article
The Human Early Maternal–Embryonic Interactome
Reprod. Med. 2023, 4(1), 40-56; https://doi.org/10.3390/reprodmed4010006 - 16 Feb 2023
Viewed by 1049
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Endometrial Physiology and Pregnancy Success)
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Case Report
A Case of Sex Discordant Dichorionic Diamniotic Twins after Single Embryo Transfer and the Importance of Zygosity Testing
Reprod. Med. 2023, 4(1), 34-39; https://doi.org/10.3390/reprodmed4010005 - 02 Feb 2023
Viewed by 990
Abstract
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 [...] Read more.
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
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Communication
Potential Association between Marital Status and Maternal and Neonatal Complications and Placental Pathology in Singleton Pregnancy
Reprod. Med. 2023, 4(1), 28-33; https://doi.org/10.3390/reprodmed4010004 - 02 Feb 2023
Viewed by 851
Abstract
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 [...] Read more.
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
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Article
A New Bioreactor to Promote Human Follicular Growth with or without Activin A in Transgender Men
Reprod. Med. 2023, 4(1), 14-27; https://doi.org/10.3390/reprodmed4010003 - 28 Jan 2023
Viewed by 897
Abstract
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 [...] Read more.
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
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