Fertility Prognosis Research Articles

7772 A Study on Role of Anti-Mullerian Hormone and Inhibin B in 46,XY Disorders Of Sexual Development

Abstract Disclosure: N. Kudugunti: None. S. Bangaru: None. R.K. Sahay: None. Background: In pre-pubertal period, a major part of the testicular tissue is constituted by Sertoli cells for which AMH, Inhibin B are specific biomarkersHigh AMH, Inhibin B levels in the prepubertal period is via FSH stimulation, which is mistakenly considered to be silent due to its reduced activity Aim & Objectives: To assess AMH and Inhibin B measurements in the diagnostic workup of prepubertal children with different subtypes of 46,XY DSD and comparing with normal controls To assess Sertoli cell function with AMH and Inhibin B and to assess correlation between testosterone elevation after hCG stimulation, basal AMH and Inhibin B Patients and methods: Pilot study-Single centered, Cross-sectional Observational study. After ethical committee approval, 40 children with 46,XY DSD & 40 healthy age matched, boys as controls recruited after taking assent. All children with DSD underwent karyotyping, assessment of hCG stimulated testosterone, DHT and androstenedione. Basal AMH and inhibin B were measured in both cases and controls. Data were analysed using IBM SPSS version 25. Results: The mean age at presentation was 4.09 years.The diagnosis was made clinically and biochemically, genetic analysis done in few patients. Out of 40 cases, 26 had normal hCG stimulated testosterone of >100 ng/dl (17 cases were 5 alpha reductase type 2 deficiency [5αR2D], 9 cases were PAIS) & 14 had low hCG stimulated testosterone of <100 ng/dl (8 cases were 17βHSD3 deficiency, 4 cases were Partial gonadal dysgenesis [PGD], 2 cases were Vanishing testis syndrome). In the low testosterone group, mean AMH in 17βHSD3 deficiency-279.95 ng/ml, in PGD-31.16 ng/ml which is statistically significant in differentiating these disorders(p-0.002)& mean Inhibin B in 17βHSD3 deficiency-186.41 pg/ml, in PGD-35.95 pg/ml which is statistically significant in differentiating these disorders (p-0.007). In vanishing testis syndrome, AMH & Inhibin B were helpful in confirming the absent functioning testicular tissue Whereas in normal testosterone group, mean AMH in PAIS-235.65 ng/ml, in 5αR2D-289.08 ng/ml difference is not statistically significant(p-0.36)& mean Inhibin B in PAIS-204.50 pg/ml, in 5αR2D-190.91 pg/ml difference is not statistically significant(p-0.72) There was significant correlation between basal AMH and hCG stimulated testosterone (r=0.434; p-0.002), Inhibin B and hCG stimulated testosterone(r=0.438; p-0.001), AMH and Inhibin B(r=0.770; p<0.001). Conclusion: AMH and Inhibin B are valuable in differentiating PGD, 17βHSD3 deficiency in low hCG stimulated testosterone patients, but not helpful in differentiating PAIS, 5αR2D in normal hCG stimulated testosterone patients. Especially in PGD they may have a role with respect to fertility prospects and malignancy risk assessment. Presentation: 6/3/2024

Analysis of Fertility Prognosis and Risk Factors in Patients Post-Gestational Trophoblastic Disease.

To retrospectively analyze the fertility outcomes and prognosis of gestational trophoblastic disease (GTD) patients, providing a basis for targeted fertility guidance and counseling. 82 GTD patients of childbearing age who received treatment at the Obstetrics and Gynecology Department of Lanzhou University First Hospital from January 2016 to January 2023 were stratified into re-pregnancy (n = 20) and non-re-pregnancy (n = 33) cohorts based on their pregnancy outcomes. The impacts of various factors on pregnancy outcomes were subsequently evaluated, encompassing the rates of subsequent pregnancies, live births, miscarriages, ectopic pregnancies, and ongoing pregnancies. Finally, logistics regression model was employed to analyze the risk factors affecting re-pregnancy in GTD patients. The study delineated those patients with different GTD pathologies had varying re-pregnancy rates (mole, erosive mole and choriocarcinoma accounted for 66.04%, 30.19% and 3.77%, respectively). Treatment predominantly involved uterine curettage, with fewer cases receiving chemotherapy alone or in conjunction with curettage accounted for 67.92%, 5.66%, and 26.42%, respectively. The average chemotherapy frequency was 4.59 ± 2.43 sessions, and a majority sought reproductive counseling. Re-pregnancy occurred in 37.74% of patients. The live birth rate was 65.00%, with miscarriage and ectopic pregnancy rates at 25.00% and 5.00% respectively. Logistic regression analysis pinpointed the absence of pre-pregnancy counseling as a significant independent risk factor for re-pregnancy in GTD patients (p < 0.05). While chemotherapy may influence ovarian function, with the majority of patients desiring children post-recovery, pregnancy rates remain high. Fertility counseling significantly enhances re-pregnancy success rates in GTD survivors, emphasizing its recommendation for those aiming to conceive post-recovery.

Dynamics of everyday practices of urban parents

In order to further improve family policy, the article aims to analyze the dynamics of everyday practices of parents. The empirical basis is the databases on individuals of the Comprehensive monitoring of living conditions (GKS-KOUZH — 2011,2016, 2018, 2020, 2022 years), which is conducted by the Federal State Statistics Service. Subsamples of urban fathers and mothers living with children under the age of 15 have been formed. The daily practices of parents are analyzed based on the indicators of work, leisure, sports, health, smoking and alcohol consumption contained in the database, depending on gender, educational level and number of children. The article presents an analysis of studies on the transmission of constructive and destructive parenting practices to children. It is shown that during the analyzed period, the proportion of parents who work in their specialty, attend various leisure facilities, participate in the activities of political and public organizations, engage in sports and drink alcohol is stable. The proportion of mothers attending religious institutions and meetings of believers has decreased. There are positive trends in a significant increase in the proportion of both fathers and mothers who are satisfied with their profession and salary, who make tourist trips, who positively assess their health and a decrease in the proportion of fathers who smoke. According to the analysis of the KOUZH-2022, more parents with higher education work in their specialty, are satisfied with wages, have the opportunity to work distantly via the Internet, practice buying food and goods over the Internet, make tourist trips, visit the theater, museums, exhibitions, restaurants, participate in social activities, do not smoke, play sports or active recreation compared to parents without higher education. Parents with many children are similar in terms of types of professional activities and level of education to one- and two-child parents. The absolute advantage of parents with many children is a significant proportion of religious fathers and the lowest level of alcohol consumption by fathers and mothers. Positive trends in the daily activities of parents inspire optimism about the prospects for fertility and the quality of parenthood.

Long-term effects on fertility after central nervous system cancer: A systematic review and meta-analysis

Abstract Background Central nervous system (CNS) cancer represents a common group of solid tumors in childhood and young adults, and less frequently in adults aged 30–40. Due to treatment advancements with increasing survival rates, disorders of the hypothalamus-pituitary axis have become increasingly relevant for patients’ future fertility plans. Most guidelines recommend that physicians should counsel their patients about fertility prognosis before initiating gonadotoxic therapy. However, for fertility preservation measures, gonadal toxicity as the only relevant risk factor has not yet been systematically reviewed. Methods A systematic literature search was performed in MEDLINE, Embase, and Cochrane in January 2024. The systematic review included studies of patients who had undergone treatment for all types of malignant CNS cancer. The outcomes were defined as clinically relevant gonadal toxicity as well as preserved fertility. The study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Results The qualitative analysis included 31 studies with a total of 4590 patients after CNS cancer. The overall pooled prevalence of gonadal toxicity was found to be 20% (95% confidence intervals [CI]: 10%–34%). Preserved fertility was present in 75% (95% CI: 64%–83%) of the patients and was maintained after at least 5 years following treatment (75%, 95% CI: 46%–91%). Conclusions This initial meta-analysis provides a basis for fertility counseling after diverse CNS cancer treatments. Due to the high heterogeneity of the study population and lack of individual patient data on fertility outcomes, it is not possible to provide an exact estimation of the fertility prognosis following a specific treatment. Thus, fertility preservation measures should still be recommended.

Oncological treatments have limited effects on the fertility prognosis in testicular cancer: A systematic review and meta-analysis.

Testicular cancer is the most common solid tumour among young men in the reproductive phase. After completing cancer treatment, up to 77% of cancer survivors report an interest in paternity after completing cancer treatment. To preserve fertility, most guidelines recommend that physicians should counsel their patients about sperm cryopreservation before initiating gonadotoxic therapy. However, few studies have assessed fertility parameters after testicular cancer therapies over the last 20 years. To close the gap of data regarding gonadotoxicity of testicular cancer therapies to enable more accurate counselling regarding fertility preservation. A systematic literature search was conducted in Medline, Embase and Cochrane until December 2022. The systematic review included studies of men who had undergone all types of unilateral testicular cancer treatment, whereas the meta-analysis excluded studies with unspecified treatments, less than 10 patients for outcome evaluation or rare tumours. Infertility (i.e. azoospermia, failure to achieve paternity or the usage of cryosperm) was defined as outcome. The qualitative analysis included 30 studies with a total of 13,718 men after unilateral testicular cancer. Treatment comprised active surveillance after unilateral orchidectomy (32.7%), radiotherapy (23.1%), standard- or low-dose chemotherapy (33.7%) and high-dose chemotherapy (1.4%). Post-treatment spermiograms were analysed in 17 studies. The quantitative synthesis included 23 studies, revealing an overall pooled prevalence of infertility (95% CI) of 14% (9%-21%). Azoospermia occurred in 8% (6%-12%). For good-prognosis patients who received standard therapy, the overall prevalence of infertility was only 4% (2%-10%). So far, this very first meta-analysis of overall infertility prevalence provides the best approximation of fertility prognosis for men who have undergone testicular cancer therapy. Despite the low prevalence of infertility, it is still recommended to undergo sperm cryopreservation because of the uncertainty of the subsequent therapy and the lack of large longitudinal data on individual treatment effects.

O-311 Oncological treatments have limited effects on the fertility prognosis in testicular cancer: A systematic review and meta-analysis

Abstract Study question What is the prevalence of infertility defined by azoospermia, failure to achieve paternity or the usage of cryosperm after oncological treatments in testicular cancer? Summary answer The overall prevalence of infertility (95% CI) is 14% (9-21%) after all therapy types and 4% (2-10%) in a pooled subgroup of good-prognosis patients. What is known already Testicular cancer is the most common solid tumor among young men in the reproductive phase between 15 and 45 years. More than 95% of the patients become long-term survivors and up to 77% of cancer survivors report an interest in paternity after completing cancer treatment. Most guidelines recommend that physicians should counsel their patients about sperm cryopreservation before initiating gonadotoxic therapy. However, few studies have assessed fertility parameters after testicular cancer therapies over the last twenty years. Thus, this very first meta-analysis in a large pooled study population of patients functions as the best approximation of fertility prognosis so far. Study design, size, duration The systematic review and meta-analysis is part of the FertiTOX project (www.fertitox.com) which aims to close the gap of data regarding gonadotoxicity of cancer therapies to enable more accurate counselling regarding fertility preservation. It was performed on all published studies since 2000 that have reported the prevalence of azoospermia, the failure to achieve a pregnancy over 12 months of regular unprotected sexual intercourse or the usage of cryosperm after oncological treatments of unilateral testicular cancer. Participants/materials, setting, methods A systematic literature search was conducted in Medline, Embase and Cochrane in December 2022. For the systematic review, studies with men after all types of unilateral testicular cancer were included. For the meta-analysis, studies with unspecified treatments, &amp;lt; 10 patients for outcome evaluation or rare tumours were excluded. Infertility was defined as azoospermia, failure to achieve paternity or the usage of cryosperm. The quality of the individual studies was assessed using the Newcastle-Ottawa Scale. Main results and the role of chance A total of 126 studies remained following screening of the abstracts and fulltext for the subject of the study. Of these, 30 studies including 13718 men with a history of unilateral testicular cancer were eligible and analysed for qualitative synthesis. Sample sizes ranged from 17 to 4846 patients with a follow-up from 1-30 (mean 6.5) years. Histology included seminomas (43.9%), non-seminomas (49.6%) and sex cord or stromal tumors (0.01%). Treatment comprised active surveillance after unilateral orchidectomy (32.7%), radiotherapy (23.1%), standard or low-dose chemotherapy (33.7%) and high-dose chemotherapy (1.4%). Spermiograms after treatment were analysed in 17 studies. A quantitative synthesis was performed in 23 studies. To account for heterogeneity observed among studies, a random-effects model was used to estimate the prevalence and its 95% CI. The overall pooled prevalence of infertility (95% CI) in men with unilateral testicular cancer after standard oncological treatment was 14% (9-21%). Azoospermia after all types of oncological treatments appeared in 8% (6-12%) of the pooled study population. For good-prognosis patients who received standard therapy (i.e. surgery with or without retroperitoneal lymph node dissection, low- or standard dosed platin-based chemotherapy up to four cycles and / or radiotherapy), the overall prevalence of infertility was only 4% (2-10%). Limitations, reasons for caution First, the majority of the studies based on either questionnaire or register data with evident selection bias. Second, further subgroup analysis was impossible due to predominantly mixed treatment cohorts allowing only an approximation of standard therapy effects. Third, infertility might have occurred due to factors besides the oncological therapy. Wider implications of the findings Our meta-analysis includes all men with fertility outcome after testicular cancer therapy. Despite the overall low prevalence of infertility, sperm cryopreservation should still be recommended since it is unclear which therapy will follow after surgery and since there is no large longitudinal data for the various individual treatment effects. Trial registration number PROSPERO (Registry number CRD42023384057)

P-364 Impact on fertility outcomes in survivors after hematopoietic stem cell transplantation for benign and malignant hematologic disorders: a systematic review and meta-analysis

Abstract Study question What is the prevalence of infertility after hematopoietic stem cell transplantation (HSCT) in females and males up to the age of 1 year? Summary answer The overall prevalence of infertility (95% CI) in women treated with HSTC is 64% (0.58-0.70) and in men 39% (0.31-0.47). What is known already HSCT is a well-established treatment that has significantly increased survival in haematological malignancies and also benign diseases since its introduction in the 1980s. The use of high-dose chemotherapy and radiotherapy, myeloablative conditioning, combined with HSCT exposes serious long-term complications, including gonadal dysfunction and infertility. The risk of ovarian and testicular damage seems to be very high. Therefore, the European Society for Blood and Marrow Transplantation (EBMT) had recommended in 2015 to consider fertility preservation measures in children and adolescents requiring HSCT. However, the data on which this recommendation was based was limited and heterogeneous. Study design, size, duration The systematic review and meta-analysis is part of the FertiTOX project (www.fertitox.com) which aims to close the gap of data regarding gonadotoxicity of cancer therapies to enable more accurate counselling regarding fertility preservation. A systematic literature search was conducted in Medline, Embase and Cochrane in November 2023, considering papers published since 2000. Participants/materials, setting, methods A total of 1632 records were identified for abstract screening. Only females and males without recurrent disease and follow up of more than one year were considered. For the systematic review, 68 studies fulfilled the criteria. For the meta-analysis, studies with &amp;lt; 10 patients were excluded. Infertility was defined in females as very low AMH, hypergonadotropic hypogonadism, amenorrhoea and/or need for hormone replacement therapy and in males as low inhibin B and/or azoospermia. Main results and the role of chance In total, 68 out of 1632 studies were included in the final analysis. Malignant diseases were mainly acute myeloid / lymphoblastic leukemia, chronic myeloid leukemia/ lymphocytic leukemia and non-hodgkin’s and hodgkin’s lymphoma. Benign diseases were sickle cell disease, Fanconi anaemia, and β-thalassemia major. In the meta-analysis, 56 studies were included, comprising 1853 female malignant cases, 241 female benign cases, 1871 male malignant cases, and 226 male benign cases. The analysis, employing a random-effects model for estimating prevalence and its 95% confidence interval, revealed that the overall pooled prevalence of infertility exceeded 30% in all groups. The prevalence of infertility was highest in female malignant cases (65%, 95% CI: 0.58-0.71). In women with benign diseases it was 61% (95% CI: 0.48-0.73). In males with malignant diseases it reached 41% (95% CI: 0.32 to 0.51) and with benign diseases 31% (95% CI: 0.19 to 0.46). Heterogeneity of data was high as shown by female as shown by the malignant cases of 83% and benign cases of 65% in women and the malignant cases of 91% and benign cases of 74% in males. Limitations, reasons for caution The heterogeneity of the included studies due to treatment variations and diverse characteristics of the study populations with large age ranges, did not allow further subgroup analyses. Thus, an individual and reliable fertility prognosis is still difficult to give. Wider implications of the findings The results of this meta-analysis support the clinical necessity of fertility preservation counselling in females and males undergoing HSCT treatment. Further prospective studies addressing the individual impact of the HSCT treatment on gonadal function are needed Trial registration number The study protocol was registered at the international Prospective Register of Systematic Reviews, PROSPERO (Registry number CRD42023486928).

O-234 Indication for fertility preservation in patients with endometriosis

Abstract Endometriosis is a complex gynecological condition that not only causes debilitating symptoms but also significantly impacts fertility. As the disease affects approximately 10% of women of reproductive age, addressing fertility preservation strategies becomes paramount. The conventional treatments for endometriosis, such as medical therapy and surgery, often fail to fully address its adverse effects on ovarian reserve and reproductive potential. Consequently, there is a growing interest in exploring fertility preservation options, particularly oocyte cryopreservation (OOC), for endometriosis patients. Despite the prevalence and impact of endometriosis on fertility, comprehensive data and guidelines specifically tailored to fertility preservation in this population remain scarce. The available evidence suggests that endometriosis, particularly when it involves ovarian endometriomas, is associated with a significant reduction in ovarian reserve, as indicated by lower levels of anti-Müllerian hormone (AMH). Surgical interventions, often necessary for managing endometriosis-related complications, can further compromise ovarian function and diminish fertility prospects. However, recent studies have shed light on the potential benefits of OOC in preserving fertility for endometriosis patients. OOC offers a minimally invasive approach with no impact on ovarian reserve compared to other fertility preservation techniques. Despite the lack of randomized controlled trials, our retrospective data have demonstrated promising outcomes, with a notable number needed to treat (NNT) of 16 for one successful pregnancy. This underscores the significance of discussing and considering OOC as part of the treatment plan for endometriosis patients, especially those at risk of ovarian compromise due to the disease or its management. The decision to pursue fertility preservation through OOC should be made on a case-by-case basis, taking into account various factors such as disease severity, patient age, ovarian reserve, and treatment history. French guidelines recommend considering OOC for endometriosis patients with bilateral ovarian endometriomas larger than 3 cm or those with endometriomas on a single ovary. Initiating fertility preservation discussions early, preferably before surgical intervention, allows patients to make informed decisions regarding their reproductive future. It is crucial to acknowledge the challenges and uncertainties associated with fertility preservation in endometriosis patients. Socio-economic factors, patient preferences, and the lack of clear criteria for selecting candidates for OOC pose significant hurdles. Furthermore, the effectiveness and cost-effectiveness of OOC in this population warrant further investigation. In addition to OOC, alternative fertility preservation options, such as ovarian tissue preservation, could be considered, particularly in cases where ovarian stimulation is not feasible or declined by the patient. However, data on the efficacy and safety of ovarian tissue preservation specifically in endometriosis patients are limited, highlighting the need for further research in this area. In conclusion, fertility preservation, particularly through OOC, holds promise for mitigating the adverse effects of endometriosis on ovarian function and fertility. While uncertainties persist, integrating fertility preservation discussions into the comprehensive management of endometriosis is essential. This ensures that patients are empowered to make informed decisions about their reproductive health and maximizes their chances of achieving desired fertility outcomes despite the challenges posed by endometriosis.

Distinct Gastrointestinal and Reproductive Microbial Patterns in Female Holobiont of Infertility.

The microbiota is in symbiosis with the human body as a holobiont. Infertility conditions affect the female reproductive tract (FRT) and its resident microbiota. However, a disturbance in homeostasis could influence the FRT and other distal body sites, such as the gastrointestinal tract (GIT). We included 21 patients with endometriosis and other infertility-associated diseases with clinical profiles and biological samples from the FRT (endometrium, endometrial fluid, and vagina), and GIT samples (oral and feces). We performed a 16S rRNA analysis of site-specific microbial communities and estimated diversity metrics. The study found body site-specific microbial patterns in the FRT-GIT. In both study groups, Lactobacillus was the most shared Amplicon Sequence Variant (ASV), a precise identifier of microbial sequences, between endometrial and vagina samples. However, shared Gardnerella and Enterobacteriaceae ASVs were linked to other conditions but not endometriosis. Remarkably, Haemophilus was a specific GIT-shared taxon in endometriosis cases. In conclusion, infertility influences distinctly the FRT and GIT microbiomes, with endometriosis showing unique microbial characteristics. We proposed the concept of 'female holobiont' as a community that comprises the host and microbes that must maintain overall homeostasis across all body sites to ensure a woman's health. Insights into these microbial patterns not only advance our understanding of the pathophysiology of infertility but also open new avenues for developing microbe-based therapeutic interventions aimed at restoring microbial balance, thereby enhancing fertility prospects.

Structural and Timing Transformations of Fertility ‒ Threats to Demographic Security of the Republic of Tatarstan

Introduction. The relevance of the article is determined by the importance of assessing the determinants of fertility to determine the possible prospects for its change and the correct justification of the directions and measures of demographic policy aimed at increasing it. The aim of the study is to identify the determinants of fertility decline in the Republic of Tatarstan in 2020‒2022 in comparison with the pre-pandemic period and to predict their impact. Materials and Methods. The authors have calculated and analyzed the dynamics of age-specific fertility rates in the Republic of Tatarstan. The influence of the structural factor and the factor of birth intensity, as well as the indirect factor ‒ age-specific marriage rates ‒ was estimated. Using the method of age movement, the dynamics of fertility and the impact of these factors on it up to 2042 were forecasted. Results. The decrease in the total fertility rate in the Republic of Tatarstan in 2020‒2022 was due to changes in the sex and age structure of the population. The excess of the total fertility rate of the region over the indicators of the Volga Federal District and the Russian Federation is due to higher total coefficients for first and second births. The difference between the average number of first births for real generations and for calendar years is determined by temporal shifts associated with postponement of first births due to late entry into first marriage and registered marriages. Discussion and Conclusion. It is predicted that the number of young people will decrease until 2028 and the number of births until 2031. The negative impact of the factor of the gender and age structure of the population will last until 2030, in the 2030s the structural factor will contribute to an increase in the overall fertility rate. The research results presented in the article can be used to determine hypotheses regarding fertility prospects when developing forecasts for demographic and socio-economic development. Correct assessment of the determinants of fertility provides grounds for the development of effective measures of demographic policy with regard to fertility.

Redox mechanisms of environmental toxicants on male reproductive function.

Humans and wildlife, including domesticated animals, are exposed to a myriad of environmental contaminants that are derived from various human activities, including agricultural, household, cosmetic, pharmaceutical, and industrial products. Excessive exposure to pesticides, heavy metals, and phthalates consequently causes the overproduction of reactive oxygen species. The equilibrium between reactive oxygen species and the antioxidant system is preserved to maintain cellular redox homeostasis. Mitochondria play a key role in cellular function and cell survival. Mitochondria are vulnerable to damage that can be provoked by environmental exposures. Once the mitochondrial metabolism is damaged, it interferes with energy metabolism and eventually causes the overproduction of free radicals. Furthermore, it also perceives inflammation signals to generate an inflammatory response, which is involved in pathophysiological mechanisms. A depleted antioxidant system provokes oxidative stress that triggers inflammation and regulates epigenetic function and apoptotic events. Apart from that, these chemicals influence steroidogenesis, deteriorate sperm quality, and damage male reproductive organs. It is strongly believed that redox signaling molecules are the key regulators that mediate reproductive toxicity. This review article aims to spotlight the redox toxicology of environmental chemicals on male reproduction function and its fertility prognosis. Furthermore, we shed light on the influence of redox signaling and metabolism in modulating the response of environmental toxins to reproductive function. Additionally, we emphasize the supporting evidence from diverse cellular and animal studies.

Implications of lifestyle factors on male reproductive health.

In recent decades, there has been a substantial decline in sperm quality in humans, with lifestyle factors playing a major role in this trend. There are several lifestyle factors which are contributing to male infertility. This review, however, discusses factors such as obesity, diet/nutrition, psychological stress, radiation exposure, cigarette smoking, and alcohol use with reference to male infertility. Sperm count, motility, morphology and sperm DNA may be adversely affected by lifestyle factors, which may also affect the endocrine regulation of reproductive function. The decline in male fertility has a significant impact on fertility rates, and the resulting implications for the human population make this a serious public health concern in the twenty-first century. Thus, lifestyle interventions through a specific framework of educational, environmental, nutritional/physical exercise, and psychological support coupled with the use of nutritional antioxidants supplements can help couples achieve better health and well-being and improve their fertility prospects or increase their chances of conception.

Treatment outcomes of tubal pregnancy with tubal preservation: A meta-analysis.

Ectopic pregnancy is a common gynecological emergency that poses a significant risk of maternal mortality during the first trimester. It also increases the incidence of infertility and repeated ectopic pregnancy. The aim of this study was to evaluate whether there is a difference in the degree of tubal patency between salpingostomy and systemic treatment with methotrexate (MTX), as well as the odds of intrauterine pregnancy and repeat ectopic pregnancy, and the degree of tubal patency in salpingectomy with or without tubal suturing. We searched PubMed, EMBASE, and the Cochrane Library up to April 2023. Four randomized controlled trials were included in the review. We analyzed the combined data using Review Manager 5.3 software and Stata 12.0 software, utilizing a random effects model. When comparing salpingostomy and systemic treatment with MTX, there was no significant difference in the degree of tubal patency (OR = 1.09, 95% CI (0.54-2.38), P = .83). For salpingostomy with or without tubal suturing, there were no significant differences in the rates of intrauterine pregnancy, repeat ectopic pregnancy, and tubal patency degree [(OR = 1.05, 95% CI (0.41-2.68), P = .92), (OR = 0.68, 95% CI (0.19-2.42), P = .92), (OR = 1.68, 95% CI (0.14-20.33), P = .68)]. This meta-analysis demonstrates that systemic treatment with MTX is an effective treatment for patients who wish to preserve their fallopian tubes without undergoing surgery. This form of treatment can help avoid surgical procedures that may damage the fallopian tubes and improve fertility prospects. If choosing surgery, we believe that opting for salpingostomy without tubal suturing could reduce the operation time and minimize damage.

Предикторы рецидивирующего течения эндометриальной гиперплазии без атипии у женщин репродуктивного возраста

Aim. To establish predictors of recurrent course of endometrial hyperplasia (EH) without atypia in women of reproductive age. Material and methods. A retrospective analysis of 180 patients of reproductive age was performed on the basis of the Department of Obstet-rics and Gynecology with a course of perinatology at the Patrice Lumumba Peoples' Friendship University of Russia in Semashko Clinical Hospital "RZD-Medicine" in 2020–2023. During the study, two cohorts of patients were formed depending on the course of EH: group 1 – the main group (n=95) was represented by patients with morphologically verified recurrent EH without atypia during a year of follow-up (1 or more episodes of relapse), group 2 – comparison (n=85) – patients with morphologically verified EH without a history of atypia, with no recurrence of hyperplasia during the year. The average age of patients in the studied cohort was 43±3.0 years (comparison groups – 40±2.0 years). Results. In a cohort of patients suffering from morphologically confirmed recurrent EH without atypia, a high incidence of the following predic-tors was established during the year: refusal/absence of medication in the anamnesis – 32.2%, duration of therapy (less than 6 months) – 23.2%, cyclic mode of progestogen use (from the 14th to the 26th day of menstrual cycle – MC/from 16 on the 26th day of the MC) – 15.8%. Patients with recurrent EH were significantly more likely to be obese in 45.3%, arterial hypertension – 38.9%, severe vitamin D deficiency – 32.6%, vitamin D deficiency – 40%, chronic endometritis – 41.1%. Conclusion. Predictors of recurrent course of EH without atypia in women of reproductive age are: refusal/absence of taking medication in anamnesis (odds ratio – OR 39.909; 95% confidence interval – CI 4.899–278.068), duration of therapy less than 6 months (OR 12.507; 95% CI 2.843–55.015), cyclic mode of progestogen use – from the 14th to the 26th day of the MC/from the 16th to the 26th day of the MC (OR 8.893; 95% CI 1.966–40.229). Patients with recurrent EH were significantly more likely to have severe vitamin D deficiency (OR 13.466; 95% CI 5.323–34.068), chronic endometritis (OR 4.237; 95% CI 2.032–8.833), hypertension (OR 3.881; 95% CI 1.858–8.801), obesity (OR 2.368; 95% CI 1.259–4.453), vitamin D deficiency (OR 1.574; 95% CI 0.814–3.045). Prevention of non-atypical hyperplasia with progestogens and lifestyle mod-ification carries a wide range of benefits, including those associated with a favorable fertility prognosis.

Home-based monitoring of ovulation to time frozen embryo transfers in the Netherlands (Antarctica-2): an open-label, nationwide, randomised, non-inferiority trial

The growing field of assisted reproductive techniques, including frozen-thawed embryo transfer (FET), should lead the way to the best sustainable health care without compromising pregnancy chances. Correct timing of FET is crucial to allow implantation of the thawed embryo. Nowadays, timing based on hospital-controlled monitoring of ovulation in the natural cycle of a woman is the preferred strategy because of the assumption of favourable fertility prospects. However, home-based monitoring is a simple method to prevent patient travel and any associated environmental concerns. We compared ongoing pregnancy rates after home-based monitoring versus hospital-controlled monitoring with ovulation triggering. This open-label, multicentre, randomised, non-inferiority trial was undertaken in 23 hospitals and clinics in the Netherlands. Women aged between 18 and 44 years with a regular ovulatory menstrual cycle were randomly assigned in a 1:1 ratio via a web-based randomisation program to home-based monitoring or hospital-controlled monitoring. Those who analysed the data were masked to the groups; those collecting the data were not. All endpoints were analysed by intention to treat and per protocol. Non-inferiority was established when the lower limit of the 90% CI exceeded -4%. This study was registered at the Dutch Trial Register (Trial NL6414). 1464 women were randomly assigned between April 10, 2018, and April 13, 2022, with 732 allocated to home-based monitoring and 732 to hospital-controlled monitoring. Ongoing pregnancy occurred in 152 (20·8%) of 732 in the home-based monitoring group and in 153 (20·9%) of 732 in the hospital-controlled monitoring group (risk ratio [RR] 0·99 [90% CI 0·81 to 1·22]; risk difference [RD] -0·14 [90% CI -3·63 to 3·36]). The per-protocol analysis confirmed non-inferiority (152 [21·0%] of 725 vs 153 [21·0%] of 727; RR 1·00 (90% CI 0·81 to 1·23); RD -0·08 [90% CI -3·60 to 3·44]). Home-based monitoring of ovulation is non-inferior to hospital-controlled monitoring of ovulation to time FET. The Dutch Organisation for Health Research and Development.

O-305 Next-generation sequencing of a cohort of 100 patients with diminished ovarian reserve reveals an etiology in 27% of cases and may predict the fertility prognosis

Abstract Study question Identify the genetic cause of a cohort of patients with unexplained Diminished ovarian reserve (DOR) by next-generation sequencing and compare with pregnancy outcome. Summary answer A high-yield positive genetic diagnosis was obtained: 27% of cases. Defects of genes involved in DNA repair/meiosis appeared to have an unfavorable prognosis. What is known already Ten percent of women undergoing Medically Assisted Procreation-MAP have a DOR defined by an AMH level &amp;lt;1.2 and an antral follicle count (AFC) &amp;lt;5. However, most causes of DOR are unknown. There is no known criteria of success in MAP. Primary ovarian insufficiency (POI) corresponds to a complete cessation of ovarian function in 1-4% of women under 40 years. We have very recently shown in a large cohort of POI that a custom-made target next-generation sequencing (NGS) POI panel allowed a genetic diagnosis in 30% of unexplained POI and leads to personalized medicine (Heddar et al., EBioMedicine. 2022 doi: 10.1016/j.ebiom.2022.104246). Study design, size, duration Prospective genetic study of a cohort of 100 patients with undergoing MAP using a custom-made NGS-POI panel comprising 88 validated POI-causing genes. These patients were for 77% European, 20% North African and 3% Asian. The classification of the variants detected were based on the American College of Medical Genetic criteria 2015. Only pathogenic and likely pathogenic variants were used for diagnosis. Candidate gene studies were performed in negative patients. Participants/materials, setting, methods One hundred patients aged 16-35 with DOR, normal karyotype and FMR1 gene, were studied with the NGS POI panel. The segregation of the variants in the available families was performed by Sanger sequencing. Cytogenetic studies of chromosomal fragility was performed if necessary. The outcome of the pregnancy (spontaneous or induced) was recorded. A correlation between the result of the genetic study and the outcome of the pregnancy has been performed. Main results and the role of chance One family included two sisters, one with POI and the other with DOR, highlighting the proximity of the two syndromes. A high positive genetic yield was found: 27% of cases. Genes were involved 1) in follicular growth and gonadal development (SOX8, AR, NOBOX, BMPR1A, BMPR1B, GNAS) (35%) 2) DNA repair (BNC1, ERCC6, BRCA1, ATM) (31%) 3) metabolism and mitochondrial functions (POLG, STAR) (12%), 4) cellular aging (24%), in particular the LMNA gene. In a patient with isolated DOR, we identified for the first time, bi-allelic truncating variants of BRCA1, a major breast/ovarian cancer susceptibility gene. Cytogenetic studies revealed increased chromosomal breaks with radial figures typical of Fanconi Anemia (FA). However there was no sign of FA or cancer in the patient and family. This observation is reminiscent of the family with isolated POI and biallelic mutations of BRCA2 (Heddar et al, J Med Genet 2021; DOI: 10.1136/jmedgenet-2019-106672). Among the 27 patients with an established genetic diagnosis, six were able to obtain a pregnancy. However, no pregnancies were achieved in the DNA repair gene suggesting an unfavorable prognosis for this gene family. On the other hand, patients with mutations of other gene families seem to have a better prognosis of fertility. Limitations, reasons for caution The size of the cohort should be implemented to confirm these results. The issues of pregnancy are not available for the whole cohort. Wider implications of the findings This is the first genetic study of a cohort of DOR and the first implication of BRCA1 in isolated DOR. It shows i) the need for genetic studies of DOR ii) the genetic link between POI and DOR iii) NGS study could give information on the fertility prognosis of DOR. Trial registration number not applicable

P-524 Fertility and subsequent pregnancy outcomes among women with tubal ectopic pregnancy treated with methotrexate

Abstract Study question What are the future fertility prospects and subsequent pregnancy outcomes among women with tubal ectopic pregnancy treated with methotrexate? Summary answer Pregnancy post-ectopic pregnancy occurred in 53% of women within 12 months following methotrexate treatment. Among those who became pregnant, ectopic pregnancy recurrence occurred in 16.8%. What is known already Concerns regarding ectopic pregnancy recurrence and future fertility predominate when counselling women about management options for tubal ectopic pregnancy treatment. Current UK National Institute for Health and Care Excellence guidance is based on low quality evidence and estimate long-term ectopic pregnancy recurrence rate of ∼18.5%. Further, they state that there are no differences in rates of subsequent pregnancy or ectopic pregnancy recurrence between ectopic pregnancy management methods. However, 30% of women managed with methotrexate experience treatment failure and require rescue surgery and subsequent pregnancy outcomes in this group are poorly understood. Study design, size, duration The data for this study were derived from a UK multicentre RCT of methotrexate and gefitinib versus methotrexate and placebo for treatment of ultrasound diagnosed definite or probable tubal ectopic pregnancy with pre-treatment hCG ≥1000 IU/L and ≤5000 IU/L (GEM3). The trial found adding gefitinib to methotrexate was not superior to placebo. This analysis reports trial participant follow-up data at 12-months examining post-treatment fertility, subsequent pregnancy outcomes and participant characteristics associated with ectopic pregnancy recurrence. Participants/materials, setting, methods Trial participants of GEM3 (as described above). Participants were contacted to provide follow-up data 12 months after randomisation to treatment. Where telephone contact was unsuccessful, electronic health records were reviewed to collect pregnancy outcome data. Post-treatment fertility and pregnancy outcomes were summarised using descriptive statistics and compared between groups using a chi-squared test, p&amp;lt;.05 signified statistical significance. Main results and the role of chance Pregnancy follow-up data was obtained for 283/327 trial participants. (167 participants were successfully contacted by telephone; the electronic health records were reviewed for 116 participants). 52.7% (149/283) of the trial participants became pregnant in the 12-month follow-up period. There was no difference in subsequent pregnancy rates between ‘methotrexate only’ and ‘methotrexate and rescue surgery’ groups. The surgical approach (salpingectomy vs salpingotomy) did not affect subsequent pregnancy rates. Among women who had a pregnancy in the follow-up period, a live birth was recorded in 65% of women (n = 93/142, n = 7 missing), any pregnancy loss (miscarriage, ectopic pregnancy, stillbirth, termination of pregnancy or molar pregnancy) was recorded in 43% of women (n = 59/137, n = 12 missing). Recurrent ectopic pregnancy was reported in 16.8% of women (n = 22/131, n = 18 missing). There was no difference in rates of live birth, pregnancy loss or recurrent ectopic pregnancy between methotrexate only and methotrexate and surgery groups or between type of surgical management groups (salpingectomy vs salpingotomy). Limitations, reasons for caution This study only reports on a 12-month follow-up period and this should be considered when interpreting comparatively low post-treatment pregnancy rates. We did not record which couples were trying-to-conceive post treatment and were therefore unable to stratify results by this variable or report subfertility rates. Wider implications of the findings This prospective dataset strengthens current understanding of the likelihood of ectopic pregnancy recurrence. Furthermore, it provides reassurance that women with tubal ectopic pregnancy managed with methotrexate requiring rescue surgery have similar post-treatment fertility and pregnancy outcomes to those successfully treated with methotrexate. Trial registration number ISRCTN67795930

Review: Evaluation of bull fertility. Functional and molecular approaches.

With the term "assisted reproduction technologies" in modern cattle farming, one could imply the collection of techniques that aim at the optimal use of bovine gametes to produce animals of high genetic value in a time- and cost-efficient manner. The accurate characterisation of sperm quality plays a critical role for the efficiency of several assisted reproduction-related procedures, such as sperm processing, in vitro embryo production and artificial insemination. Bull fertility is ultimately a collective projection of the ability of a series of ejaculates to endure sperm processing stress, and achieve fertilisation of the oocyte and production of a viable and well-developing embryo. In this concept, the assessment of sperm functional and molecular characteristics is key to bull fertility diagnostics and prognostics. Among others, functional features linked to sperm plasma membrane, acrosome and DNA integrity are usually assessed as a measure of the ability of sperm to express the phenotypes that will allow them to maintain their homeostasis and orchestrate-in a strict temporal manner-the course of events that will enable the delivery of their genetic content to the oocyte upon fertilisation. Nevertheless, measures of sperm functionality are not always adequate indicators of bull fertility. Nowadays, advancements in the field of molecular biology have facilitated the profiling of several biomolecules in male gametes. The molecular profiling of bovine sperm offers a deeper insight into the mechanisms underlying sperm physiology and, thus, can reveal novel candidate markers for bull fertility prognosis. In this review, the importance of three organelles (the nucleus, the plasma membrane and the acrosome) for the characterisation of sperm fertilising capacity and bull fertility is discussed at functional and molecular levels. In particular, information about sperm head morphometry, chromatin structure, viability as well as the ability of sperm to capacitate and undergo the acrosome reaction are presented in relation to the cryotolerance of male gametes and bull fertility. Finally, major spermatozoal coding and non-coding RNAs, and proteins that are involved in the above-mentioned aspects of sperm functionality are also summarised.

Family building after diagnosis of premature ovarian insufficiency: a cross-sectional survey in 324 women.

The diagnosis of premature ovarian insufficiency (POI) is a traumatic event for many patients that involves poor fertility prognosis. After such diagnosis, spontaneous pregnancies are rare. The alternatives for building a family are oocyte donation, embryo donation, and adoption. However, we have few information on how many women with POI finally built a family after the diagnosis and which alternative they chose. We performed a cross-sectional, descriptive study. We conducted a survey of all the women who consulted for POI in the department of endocrinology and reproductive medicine at la Pitié Salpêtrière between May 31, 1991, and January 12, 2021. We included patients who continued to be followed up regularly by our department or were contacted by mail or phone between June and September 2021. We excluded patients with Turner syndrome and POI secondary to oncological treatment and patients under 18 at the time of the survey. 985 patients were referred to the department for POI, and 324 patients were finally analyzed. 41% of the women who wanted to build a family had children after the diagnosis: 53.9% by oocyte donation, 1 woman by embryo donation, 5.6% after ovarian stimulation, 13.5% by adoption, and 25.8% who had spontaneous pregnancy after a mean time of 2.5 years. Spontaneous pregnancy rate was 8.6% in the whole cohort. Having children after a diagnosis of POI is not uncommon but more often results from oocyte donation. This study will provide enlightened information for newly diagnosed women on the possibilities to build a family after POI diagnosis.

The impact of primary ciliary dyskinesia on female and male fertility: a narrative review.

Primary ciliary dyskinesia (PCD) is a genetic condition affecting the structure and function of sperm flagellum and motile cilia including those in the male and female reproductive tracts. Infertility is a commonly reported feature of PCD, but there is uncertainty as to how best to counsel patients on their fertility prognosis. This review aimed to summarize the prevalence of subfertility, possible underlying mechanisms, and the success of ART in men and women with PCD. The efficacy of ART in this patient group is relatively unknown and, hence, the management of infertility in PCD patients remains a challenge. There are no previous published or registered systematic reviews of fertility outcomes in PCD. Systematic literature searches were performed in Medline, Embase, Cochrane Library, and PubMed electronic databases to identify publications between 1964 and 2022 reporting fertility outcomes in men and women with PCD. Publications were excluded if they reported only animal studies, where gender was not specified or where subjects had a medical co-morbidity also known to impact fertility. Quality of evidence was assessed by critical appraisal and application of an appraisal tool for cross-sectional studies. The primary outcomes were natural conception in men and women with PCD, and conception following ART in men and women with PCD. A total of 1565 publications were identified, and 108 publications were included after screening by two independent researchers. The quality of available evidence was low. The exact prevalence of subfertility in PCD is unclear but appears to be higher in men (up to 83% affected) compared to women (up to 61% affected). Variation in the prevalence of subfertility was observed between geographic populations which may be explained by differences in underlying genotype and cilia function. Limited evidence suggests subfertility in affected individuals is likely caused by abnormal cilia motion in the fallopian tubes, endometrium and efferent ductules, and dysmotile sperm. Some men and women with PCD benefited from ART, which suggests its use should be considered in the management of subfertility in this patient group. Further epidemiological and controlled studies are needed to determine the predictors of fertility and optimal management in this patient group. It is important that patients with PCD receive evidence-based counselling about the potential impact of their condition on their fertility prognosis and what management options may be available to them if affected. Understanding the pathophysiology and optimal management of subfertility in PCD will increase our understanding of the role of cilia and the impact of wider secondary ciliopathies on reproduction.