[Artificial intelligence: to a better predictive strategy for testicular sperm extraction outcome in azoospermia]. / Intelligence artificielle : vers une meilleure stratégie de prédiction du résultat de la biopsie testiculaire dans un contexte d'azoospermie.

Azoospermia, defined as the absence of sperm in the semen, is found in 10-15 % of infertile patients. Two-thirds of these cases are caused by impaired spermatogenesis, known as non-obstructive azoospermia (NOA). In this context, surgical sperm extraction using testicular sperm extraction (TESE) is the best option and can be offered to patients as part of fertility preservation, or to benefit from in vitro fertilization. The aim of the preoperative assessment is to identify the cause of NOA and evaluate the status of spermatogenesis. Its capacity to predict TESE success remains limited. As a result, no objective and reliable criteria are currently available to guide professionals on the chances of success and enable them to correctly assess the benefit-risk balance of this procedure. Artificial intelligence (AI), a field of research that has been rapidly expanding in recent years, has the potential to revolutionize medicine by making it more predictive and personalized. The aim of this review is to introduce AI and its key concepts, and then to examine the current state of research into predicting the success of TESE.

Ovarian reserve in patients with FMR1 gene premutation and the role of fertility preservation.

INTRODUCTION: Women with premutation (PM) of the FMR1 gene may suffer from reduced ovarian reserve or even premature ovarian insufficiency (POI). We studied hormonal and ultrasound ovarian reserve, fertility and fertility preservation outcomes in these patients. PATIENTS AND METHOD: Retrospective cohort study of 63 female FMR1 premutation carriers. RESULTS: Sixty-three female patients bearing an FMR1 premutation were included. Median age was 30 years [26.5-35]. Median number of CGG triplets was 83 [77.2-92]. Before diagnosis of PM, 19 women (30%) had had in all 35 pregnancies, resulting in 20 births, including 7 affected children. After diagnosis of PM, 17 women (26.1%) had in all 23 pregnancies, at a median age of 34.5 years [32.2-36.0]: 2 after preimplantation genetic diagnosis, 3 after oocyte donation, 18 spontaneously, and 5 ending in medical termination for Fragile X syndrome. Thirty-three patients (52.4%) had POI diagnosis (median age, 30 years [27-34]) with median FSH level 84 IU/L [50.5-110] and median AMH level 0.08 ng/ml [0.01-0.19]. After POI diagnosis, 8 women had in all 9 pregnancies: 3 following oocyte donation, and 6 spontaneous in 5 women (15.1%). Eight of the 9 pregnancies resulted in a live birth (including 2 affected children) and 1 in medical termination for trisomy 13. The median age of the 30 patients without POI was 31 years [25.2-35.0]. Thirteen women (20.6%) underwent fertility preservation, at a median age of 29 years [24-33]: FSH 7.7 IU/L [6.8-9.9], AMH 1.1 ng/mL [0.95-2.1], antral follicle count 9.5 [7.7-14.7]. A median 15 oocytes [10-26] were cryopreserved in a median 2 cycles [1-3]. At the time of writing, no oocytes had yet been thawed for in vitro fertilization. CONCLUSIONS: This study shows the importance of early fertility preservation after diagnosis of FMR1 premutation in women, due to early deterioration of ovarian reserve. Genetic counseling is essential in these patients, as spontaneous pregnancies are not uncommon, even in cases of impaired ovarian reserve, and can lead to birth of affected children.

[First-line management of infertile couple. Guidelines for clinical practice of the French College of Obstetricians and Gynecologists 2022]. / Prise en charge de première intention du couple infertile : mise à jour des RPC 2010 du CNGOF.

OBJECTIVE: To update the 2010 CNGOF clinical practice guidelines for the first-line management of infertile couples. MATERIALS AND METHODS: Five major themes (first-line assessment of the infertile woman, first-line assessment of the infertile man, prevention of exposure to environmental factors, initial management using ovulation induction regimens, first-line reproductive surgery) were identified, enabling 28 questions to be formulated using the Patients, Intervention, Comparison, Outcome (PICO) format. Each question was addressed by a working group that had carried out a systematic review of the literature since 2010, and followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) methodology to assess the quality of the scientific data on which the recommendations were based. These recommendations were then validated during a national review by 40 national experts. RESULTS: The fertility work-up is recommended to be prescribed according to the woman's age: after one year of infertility before the age of 35 and after 6months after the age of 35. A couple's initial infertility work-up includes a single 3D ultrasound scan with antral follicle count, assessment of tubal permeability by hysterography or HyFOSy, anti-Mullerian hormone assay prior to assisted reproduction, and vaginal swabbing for vaginosis. If the 3D ultrasound is normal, hysterosonography and diagnostic hysteroscopy are not recommended as first-line procedures. Chlamydia trachomatis serology does not have the necessary performance to predict tubal patency. Post-coital testing is no longer recommended. In men, spermogram, spermocytogram and spermoculture are recommended as first-line tests. If the spermogram is normal, it is not recommended to check the spermogram. If the spermogram is abnormal, an examination by an andrologist, an ultrasound scan of the testicles and hormonal test are recommended. Based on the data in the literature, we are unable to recommend a BMI threshold for women that would contraindicate medical management of infertility. A well-balanced Mediterranean-style diet, physical activity and the cessation of smoking and cannabis are recommended for infertile couples. For fertility concern, it is recommended to limit alcohol consumption to less than 5 glasses a week. If the infertility work-up reveals no abnormalities, ovulation induction is not recommended for normo-ovulatory women. If intrauterine insemination is indicated based on an abnormal infertility work-up, gonadotropin stimulation and ovulation monitoring are recommended to avoid multiple pregnancies. If the infertility work-up reveals no abnormality, laparoscopy is probably recommended before the age of 30 to increase natural pregnancy rates. In the case of hydrosalpinx, surgical management is recommended prior to ART, with either salpingotomy or salpingectomy depending on the tubal score. It is recommended to operate on polyps>10mm, myomas 0, 1, 2 and synechiae prior to ART. The data in the literature do not allow us to systematically recommend asymptomatic uterine septa and isthmoceles as first-line surgery. CONCLUSION: Based on strong agreement between experts, we have been able to formulate updated recommendations in 28 areas concerning the initial management of infertile couples.

Is large for gestational age in singletons born after frozen embryo transfer associated with freezing technique or endometrial preparation protocol? A longitudinal national French study.

STUDY QUESTION: Is large for gestational age (LGA) observed in babies born after frozen embryo transfer (FET) associated with either the freezing technique or the endometrial preparation protocol? SUMMARY ANSWER: Artificial cycles are associated with a higher risk of LGA, with no difference in rate between the two freezing techniques (vitrification versus slow freezing) or embryo stage (cleaved embryo versus blastocyst). WHAT IS KNOWN ALREADY: Several studies have compared neonatal outcomes after fresh embryo transfer (ET) and FET and shown that FET is associated with improved neonatal outcomes, including reduced risks of preterm birth, low birthweight, and small for gestational age (SGA), when compared with fresh ET. However, these studies also revealed an increased risk of LGA after FET. The underlying pathophysiology of this increased risk remains unclear; parental infertility, laboratory procedures (including embryo culture conditions and freezing-thawing processes), and endometrial preparation treatments might be involved. STUDY DESIGN, SIZE, DURATION: A multicentre epidemiological data study was performed through a retrospective analysis of the standardized individual clinical records of the French national register of IVF from 2014 to 2018, including single deliveries resulting from fresh ET or FET that were prospectively collected in fertility centres. Complementary data were collected from the participating fertility centres and included the vitrification media and devices, and the endometrial preparation protocols. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were collected from 35 French ART centres, leading to the inclusion of a total of 72 789 fresh ET, 10 602 slow-freezing FET, and 39 062 vitrification FET. Main clinical outcomes were presented according to origin of the transferred embryos (fresh, slow frozen, or vitrified embryos) and endometrial preparations for FET (ovulatory or artificial cycles), comparing five different groups (fresh, slow freezing-ovulatory cycle, slow freezing-artificial cycle, vitrification-ovulatory cycle, and vitrification-artificial cycle). Foetal growth disorders were defined in live-born singletons according to gestational age and sex-specific weight percentile distribution: SGA and LGA if <10th and ≥90th percentiles, respectively. Analyses were performed using linear mixed models with the ART centres as random effect. MAIN RESULTS AND THE ROLE OF CHANCE: Transfers led to, respectively, 19 006, 1798, and 9195 deliveries corresponding to delivery rates per transfer of 26.1%, 17.0%, and 23.5% after fresh ET, slow-freezing FET, and vitrification FET, respectively. FET cycles were performed in either ovulatory cycles (n = 21 704) or artificial cycles (n = 34 237), leading to 5910 and 10 322 pregnancies, respectively, and corresponding to pregnancy rates per transfer of 31.6% and 33.3%. A significantly higher rate of spontaneous miscarriage was observed in artificial cycles when compared with ovulatory cycles (33.3% versus 21.4%, P < 0.001, in slow freezing groups and 31.6% versus 21.8%, P < 0.001 in vitrification groups). Consequently, a lower delivery rate per transfer was observed in artificial cycles compared with ovulatory cycles both in slow freezing and vitrification groups (15.5% versus 18.9%, P < 0.001 and 22.8% versus 24.9%, P < 0.001, respectively). Among a total of 26 585 live-born singletons, 16 413 babies were born from fresh ET, 1644 from slow-freezing FET, and 8528 from vitrification FET. Birthweight was significantly higher in the FET groups than in the fresh ET group, with no difference between the two freezing techniques. Likewise, LGA rates were higher and SGA rates were lower in the FET groups compared with the fresh ET group whatever the method used for embryo freezing. In a multivariable analysis, the risk of LGA following FET was significantly increased in artificial compared with ovulatory cycles. In contrast, the risk of LGA was not associated with either the freezing procedure (vitrification versus slow freezing) or the embryo stage (cleaved embryo versus blastocyst) at freezing. Regarding the vitrification method, the risk of LGA was not associated with either the vitrification medium used or the embryo stage. LIMITATIONS, REASONS FOR CAUTION: No data were available on maternal context, such as parity, BMI, infertility cause, or maternal comorbidities, in the French national database. In particular, we cannot exclude that the increased risk of LGA observed following FET with artificial cycles may, at least partially, be associated with a confounding effect of some maternal factors. No information about embryo culture and incubation conditions was available. Most of the vitrification techniques were performed using the same device and with two main vitrification media, limiting the validity of a comparison of risk for LGA according to the device or vitrification media used. WIDER IMPLICATIONS OF THE FINDINGS: Our results seem reassuring, since no potential foetal growth disorders following embryo vitrification in comparison with slow freezing were observed. Even if other factors are involved, the endometrial preparation treatment seems to have the greatest impact on LGA risk following FET. FET during ovulatory cycles could minimize the risk for foetal growth disorders. STUDY FUNDING/COMPETING INTEREST(S): This work has received funding from the French Biomedicine Agency (Grant number: 19AMP002). None of the authors has any conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Do IVF culture conditions have an impact on neonatal outcomes? A systematic review and meta-analysis.

PURPOSE: Are embryo culture conditions, including type of incubator, oxygen tension, and culture media, associated with obstetric or neonatal complications following in vitro fertilization (IVF)? METHODS: A systematic search of MEDLINE, EMBASE, and Cochrane Library was performed from January 01, 2008, until October 31, 2021. The studies reporting quantitative data on at least one of the primary outcomes (birthweight and preterm birth) for the exposure group and the control group were included. For oxygen tension, independent meta-analysis was performed using Review Manager, comparing hypoxia/normoxia. For culture media, a network meta-analysis was carried out using R software, allowing the inclusion of articles comparing two or more culture media. RESULTS: After reviewing 182 records, 39 full-text articles were assessed for eligibility. A total of 28 studies were kept for review. Meta-analysis about the impact of incubator type on perinatal outcomes could not be carried out because of a limited number of studies. For oxygen tension, three studies were included. The pairwise meta-analysis comparing hypoxia/normoxia did not show any statistical difference for birthweight and gestational age at birth. For culture media, 18 studies were included. The network meta-analysis failed to reveal any significant impact of different culture media on birthweight or preterm birth. CONCLUSION: No difference was observed for neonatal outcomes according to the embryo culture conditions evaluated in this review. Further research is needed about the safety of IVF culture conditions as far as future children's health is concerned.

[The revision of the Bioethics Act, two years on: major principles and consequences for practice in the reproductive biology laboratory]. / La révision de la loi de bioéthique, deux ans après : grands principes et conséquences pour la pratique au laboratoire de biologie de la reproduction.

Since 1994, in France, bioethics law has set the regulatory framework for Medically Assisted Reproduction (MAR). The latest revision of the law of August 2, 2021, is characterized by major upheavals in the field of MAR and intervenes in several areas: the purpose and conditions to access to MAR, access to origins in the case of gamete or embryo donation, and gametes cryopreservation without medical indication. Indeed, the law authorizes, because of a strong societal demand, the extension of sperm donation to couples of women and unmarried women, as well as the possibility for any person to preserve his/her gametes if he/she meets the age criteria defined by decree. Finally, the law opens the possibility for people born following gamete or embryo donation to have access, from their 18th anniversary, to identifying and/or non-identifying data. These new measures have led to a very important number of MAR requests to fertility and donation centers, and have required the implementation of new circuits in order to harmonize care, without discrimination or prioritization.

Impact of testicular cancer on sperm small non-coding RNA signature: a pilot study.

Testicular germ cell tumours (TGCTs) are the most common tumours in young adults of European ancestry. The high heritability and the constantly increased incidence, which has doubled over the last 20 years, strongly suggest that both genetic and environmental factors are likely to shape the TGCT susceptibility. While genome-wide association studies have identified loci associated with TGCT susceptibility, the role played by environmental molecular vectors in TGCT susceptibility remains unclear. Evidence shows that sperm non-coding RNAs provide a good vision of the environmental stresses experienced by men. Here, to determine whether TGCT impacts the abundance of specific non-coding RNAs in sperm, small RNA deep sequencing analysis of sperm of 25 men aged between 19 and 42 years, diagnosed with (n = 16) or without (n = 9) TGCT was performed. The primary analysis showed no statistical significance in the sncRNA population between the TGCT and non-TGCT groups. However, when sperm physiological parameters were considered to look for differentially expressed sncRNA, we evidenced 11 differentially expressed sncRNA between patients and control which allow a clear discrimination between control and TGCT samples after Hierarchical Clustering analysis. Together, these findings indicate that sperm small non-coding RNAs abundance may have the potential for diagnosing men with TGCT. However, specific care should be taken regarding sperm physiological parameters of the TGCT patients. Hence, larger studies are needed to confirm our findings and to determine whether such a signature associates with the risks to develop TGCT.

Higher risk of pre-eclampsia and other vascular disorders with artificial cycle for frozen-thawed embryo transfer compared to ovulatory cycle or to fresh embryo transfer following in vitro fertilization.

Background: Risks of maternal morbidity are known to be reduced in pregnancies resulting from frozen embryo transfer (FET) compared to fresh-embryo transfer (fresh-ET), except for the risk of pre-eclampsia, reported to be higher in FET pregnancies compared to fresh-ET or natural conception. Few studies have compared the risk of maternal vascular morbidities according to endometrial preparation for FET, either with ovulatory cycle (OC-FET) or artificial cycle (AC-FET). Furthermore, maternal pre-eclampsia could be associated with subsequent vascular disorders in the offspring. Methods: A 2013-2018 French nationwide cohort study comparing maternal vascular morbidities in 3 groups of single pregnancies was conducted: FET with either OC or AC preparation, and fresh-ET. Data were extracted from the French National Health System database. Results were adjusted for maternal characteristics and infertility (age, parity, smoking, obesity, history of diabetes or hypertension, endometriosis, polycystic ovary syndrome and premature ovarian insufficiency). Results: A total of 68025 single deliveries were included: fresh-ET (n=48152), OC-FET (n=9500), AC-FET (n=10373). The risk of pre-eclampsia was higher in AC-FET compared to OC-FET and fresh-ET groups in univariate analysis (5.3% vs. 2.3% and 2.4%, respectively, P<0.0001). In multivariate analysis the risk was significantly higher in AC-FET compared to fresh-ET: aOR=2.43 [2.18-2.70], P<0.0001). Similar results were observed for the risk of other vascular disorders in univariate analysis (4.7% vs. 3.4% and 3.3%, respectively, P=0.0002) and in multivariate analysis (AC-FET compared to fresh-ET: aOR=1.50 [1.36-1.67], P<0.0001). In multivariate analysis, the risk of pre-eclampsia and other vascular disorders were comparable in OC-FET and fresh-ET: aOR=1.01 [0.87-1.17, P= 0.91 and aOR=1.00 [0.89-1.13], P=0.97, respectively).Within the group of FET, the risks of pre-eclampsia and other vascular disorders in multivariate analysis were higher in AC-FET compared to OC-FET (aOR=2.43 [2.18-2.70], P<0.0001 and aOR=1.5 [1.36-1.67], P<0.0001, respectively). Conclusion: This nationwide register-based cohort study highlights the possibly deleterious role of prolonged doses of exogenous estrogen-progesterone supplementation on gestational vascular pathologies and the protective role of the corpus luteum present in OC-FET for their prevention. Since OC-FET has been demonstrated not to strain the chances of pregnancy, OC preparation should be advocated as first-line preparation in FET as often as possible in ovulatory women.

A Machine Learning Approach for the Prediction of Testicular Sperm Extraction in Nonobstructive Azoospermia: Algorithm Development and Validation Study.

BACKGROUND: Testicular sperm extraction (TESE) is an essential therapeutic tool for the management of male infertility. However, it is an invasive procedure with a success rate up to 50%. To date, no model based on clinical and laboratory parameters is sufficiently powerful to accurately predict the success of sperm retrieval in TESE. OBJECTIVE: The aim of this study is to compare a wide range of predictive models under similar conditions for TESE outcomes in patients with nonobstructive azoospermia (NOA) to identify the correct mathematical approach to apply, most appropriate study size, and relevance of the input biomarkers. METHODS: We analyzed 201 patients who underwent TESE at Tenon Hospital (Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris), distributed in a retrospective training cohort of 175 patients (January 2012 to April 2021) and a prospective testing cohort (May 2021 to December 2021) of 26 patients. Preoperative data (according to the French standard exploration of male infertility, 16 variables) including urogenital history, hormonal data, genetic data, and TESE outcomes (representing the target variable) were collected. A TESE was considered positive if we obtained sufficient spermatozoa for intracytoplasmic sperm injection. After preprocessing the raw data, 8 machine learning (ML) models were trained and optimized on the retrospective training cohort data set: The hyperparameter tuning was performed by random search. Finally, the prospective testing cohort data set was used for the model evaluation. The metrics used to evaluate and compare the models were the following: sensitivity, specificity, area under the receiver operating characteristic curve (AUC-ROC), and accuracy. The importance of each variable in the model was assessed using the permutation feature importance technique, and the optimal number of patients to include in the study was assessed using the learning curve. RESULTS: The ensemble models, based on decision trees, showed the best performance, especially the random forest model, which yielded the following results: AUC=0.90, sensitivity=100%, and specificity=69.2%. Furthermore, a study size of 120 patients seemed sufficient to properly exploit the preoperative data in the modeling process, since increasing the number of patients beyond 120 during model training did not bring any performance improvement. Furthermore, inhibin B and a history of varicoceles exhibited the highest predictive capacity. CONCLUSIONS: An ML algorithm based on an appropriate approach can predict successful sperm retrieval in men with NOA undergoing TESE, with promising performance. However, although this study is consistent with the first step of this process, a subsequent formal prospective multicentric validation study should be undertaken before any clinical applications. As future work, we consider the use of recent and clinically relevant data sets (including seminal plasma biomarkers, especially noncoding RNAs, as markers of residual spermatogenesis in NOA patients) to improve our results even more.

Fetal growth disorders following medically assisted reproduction: due to maternal context or techniques? A national French cohort study.

RESEARCH QUESTION: What part do maternal context and medically assisted reproduction (MAR) techniques play in the risk of fetal growth disorders? DESIGN: This retrospective nationwide cohort study uses data available in the French National Health System database and focuses on the period from 2013 to 2017. Fetal growth disorders were divided into four groups according to the origin of pregnancy: fresh embryo transfer (n = 45,201), frozen embryo transfer (FET, n = 18,845), intrauterine insemination (IUI, n = 20,179) and natural conceptions (n = 3,412,868). Fetal growth disorders were defined from the percentiles of the weight distribution according to gestational age and sex: small and large for gestational age (SGA and LGA) if <10th and >90th percentiles, respectively. Analyses were performed using univariate and multivariate logistic models. RESULTS: Compared with births following natural conception, multivariate analysis showed that the risk of SGA was higher for births following fresh embryo transfer and IUI (adjusted odds ratio [aOR] 1.26 [1.22-1.29] and 1.08 [1.03-1.12], respectively) and significantly lower following FET (aOR 0.79 [0.75-0.83]). The risk of LGA was higher for births following FET (aOR 1.32 [1.27-1.38]), especially in artificial cycles when compared with ovulatory cycles (aOR 1.25 [1.15-1.36]). In the subgroup of births without any obstetrical or neonatal morbidity, the same increased risk of SGA and LGA were observed following fresh embryo transfer or IUI and FET (aOR 1.23 [1.19-1.27] or 1.06 [1.01-1.11] and aOR 1.36 [1.30-1.43], respectively). CONCLUSIONS: An effect of MAR techniques on the risks for SGA and LGA is suggested independently from maternal context and obstetrical or neonatal morbidities. Pathophysiological mechanisms remain poorly understood and should be further evaluated, as well as the influence of embryonic stage and freezing techniques.

Influence of breast cancer prognostic factors on oocyte in vitro maturation outcomes performed for urgent fertility preservation.

STUDY QUESTION: Do breast cancer (BC) characteristics influence IVM of oocytes outcomes in patients undergoing fertility preservation (FP)? SUMMARY ANSWER: Scarff-Bloom-Richardson (SBR) III grade, triple-negative BC and HER2 overexpression are independent predictors of fewer oocytes or poor IVM outcomes in young women seeking FP. WHAT IS KNOWN ALREADY: SBR grade, triple-negative status and overexpression of HER2, as well as a high Ki67 proliferation index are all established prognostic factors for BC, influencing patients' therapeutic management. Yet there are also concerns about the potential impact of cancer status on ovarian reserve and function. Previous studies analysing the results of ovarian stimulation in BC patients have shown conflicting findings. Nevertheless, there is no data on the potential impact of BC status and prognostic factors on IVM outcome in women undergoing urgent FP. STUDY DESIGN, SIZE, DURATION: We studied 321 BC patients, 18 to 41 years of age, who were also candidates for oocyte cryopreservation following IVM. The number of oocytes recovered, maturation rate and total number of cryopreserved oocytes were assessed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian reserve markers (antral follicle count [AFC] and serum anti-Müllerian hormone [AMH] levels) and IVM outcomes were compared according to BC characteristics (Ki67 proliferation index >20%, progesterone and/or oestrogen receptors expression, HER2 status and SBR grade). Logistic regression analysis was then performed to determine the variables that could be independently associated with poor IVM outcomes, such as oocyte retrieval rate <50%, oocyte maturation rate <60% and total number of frozen oocytes <5. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, the mean age of the population was 32.3 ± 4.1 years. Mean AFC and serum AMH levels were 22.8 ± 13.9 follicles and 3.8 ± 3.1 ng/ml, respectively. AMH levels were significantly lower in case of triple-negative BC when compared with ER/PR/HER2 status positive cancer (3.1 ± 2.6 ng/ml vs 4.0 ± 3.3 ng/ml, P = 0.02). The mean number of recovered oocytes was 10.2 ± 9.1. After a mean maturation rate of 58.0 ± 26.1%, 5.8 ± 5.3 mature oocytes were cryopreserved per cycle. The number of retrieved and cryopreserved oocytes after IVM were significantly lower in patients presenting with an SBR III tumour when compared with an SBR I or II tumour (9.6 ± 8.7 vs 11.7 ± 9.8, P = 0.02 and 5.4 ± 5.4 vs 6.6 ± 5.8, P = 0.02, respectively). Multivariate statistical analysis showed that HER2 positive status was associated with a mean maturation rate <60% (odds ratio: 0.54; 95% CI (0.30-0.97)). Ki67 and hormonal status were not correlated with poor IVM outcomes. LIMITATIONS, REASONS FOR CAUTION: A weakness is the retrospective nature of the study. Moreover, as with many studies focusing on FP in oncology patients, the lack of data after reutilization of IVM oocytes prevents drawing reliable conclusions on the fate of these frozen gametes. WIDER IMPLICATIONS OF THE FINDINGS: BC prognostic factors might influence IVM outcomes. Moreover, HER2 is likely to be involved in the ovarian function and oocyte maturation process. Further investigations are needed to better understand the mechanisms at play and their possible impact on the competence of IVM oocytes. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was used and there are no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Testicular sperm extraction (TESE) outcomes in the context of malignant disease: a systematic review.

Advances in the oncology field have led to improved survival rates. Consequently, quality of life after remission is anticipated, which includes the possibility to conceive children. Since cancer treatments are potentially gonadotoxic, fertility preservation must be proposed. Male fertility preservation is mainly based on ejaculated sperm cryopreservation. When this is not possible, testicular sperm extraction (TESE) may be planned. To identify situations in which TESE has been beneficial, a systematic review was conducted. The search was carried out on the PubMed, Scopus, Google Scholar, and CISMeF databases from 1 January 2000 to 19 March 2020. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations were followed in selecting items of interest. Thirty-four articles were included in the systematic review, including 15 articles on oncological testicular sperm extraction (oncoTESE), 18 articles on postgonadotoxic treatment TESE and 1 article on both oncoTESE and postgonadotoxic treatment TESE. Testicular sperm freezing was possible for 42.9% to 57.7% of patients before gonadotoxic treatment and for 32.4% to 75.5% of patients after gonadotoxic treatment, depending on the type of malignant disease. Although no formal conclusion could be drawn about the chances to obtain sperm in specific situations, our results suggest that TESE can be proposed before and after gonadotoxic treatment. Before treatment, TESE is more often proposed for men with testicular cancer presenting with azoospermia since TESE can be performed simultaneously with tumor removal or orchiectomy. After chemotherapy, TESE may be planned if the patient presents with persistent azoospermia.

Obstetrical outcomes and maternal morbidities associated with COVID-19 in pregnant women in France: A national retrospective cohort study.

BACKGROUND: To the best of our knowledge, no study has exhaustively evaluated the association between maternal morbidities and Coronavirus Disease 2019 (COVID-19) during the first wave of the pandemic in pregnant women. We investigated, in natural conceptions and assisted reproductive technique (ART) pregnancies, whether maternal morbidities were more frequent in pregnant women with COVID-19 diagnosis compared to pregnant women without COVID-19 diagnosis during the first wave of the COVID-19 pandemic. METHODS AND FINDINGS: We conducted a retrospective analysis of prospectively collected data in a national cohort of all hospitalizations for births ≥22 weeks of gestation in France from January to June 2020 using the French national hospitalization database (PMSI). Pregnant women with COVID-19 were identified if they had been recorded in the database using the ICD-10 (International Classification of Disease) code for presence of a hospitalization for COVID-19. A total of 244,645 births were included, of which 874 (0.36%) in the COVID-19 group. Maternal morbidities and adverse obstetrical outcomes among those with or without COVID-19 were analyzed with a multivariable logistic regression model adjusted on patient characteristics. Among pregnant women, older age (31.1 (±5.9) years old versus 30.5 (±5.4) years old, respectively, p < 0.001), obesity (0.7% versus 0.3%, respectively, p < 0.001), multiple pregnancy (0.7% versus 0.4%, respectively, p < 0.001), and history of hypertension (0.9% versus 0.3%, respectively, p < 0.001) were more frequent with COVID-19 diagnosis. Active smoking (0.2% versus 0.4%, respectively, p < 0.001) and primiparity (0.3% versus 0.4%, respectively, p < 0.03) were less frequent with COVID-19 diagnosis. Frequency of ART conception was not different between those with and without COVID-19 diagnosis (p = 0.28). When compared to the non-COVID-19 group, women in the COVID-19 group had a higher frequency of admission to ICU (5.9% versus 0.1%, p < 0.001), mortality (0.2% versus 0.005%, p < 0.001), preeclampsia/eclampsia (4.8% versus 2.2%, p < 0.001), gestational hypertension (2.3% versus 1.3%, p < 0.03), postpartum hemorrhage (10.0% versus 5.7%, p < 0.001), preterm birth at <37 weeks of gestation (16.7% versus 7.1%, p < 0.001), <32 weeks of gestation (2.2% versus 0.8%, p < 0.001), <28 weeks of gestation (2.4% versus 0.8%, p < 0.001), induced preterm birth (5.4% versus 1.4%, p < 0.001), spontaneous preterm birth (11.3% versus 5.7%, p < 0.001), fetal distress (33.0% versus 26.0%, p < 0.001), and cesarean section (33.0% versus 20.2%, p < 0.001). Rates of pregnancy terminations ≥22 weeks of gestation, stillbirths, gestational diabetes, placenta praevia, and placenta abruption were not significantly different between the COVID-19 and non-COVID-19 groups. The number of venous thromboembolic events was too low to perform statistical analysis. A limitation of this study relies in the possibility that asymptomatic infected women were not systematically detected. CONCLUSIONS: We observed an increased frequency of pregnant women with maternal morbidities and diagnosis of COVID-19 compared to pregnant women without COVID-19. It appears essential to be aware of this, notably in populations at known risk of developing a more severe form of infection or obstetrical morbidities and in order for obstetrical units to better inform pregnant women and provide the best care. Although causality cannot be determined from these associations, these results may be in line with recent recommendations in favor of vaccination for pregnant women.

Reproductive functions and fertility preservation in transgender women: a French case series.

RESEARCH QUESTION: The reproductive potential of transgender people may be impaired by gender-affirming hormone treatment (GAHT) and is obviously suppressed by gender-affirming surgery involving bilateral orchiectomy. The evolution of medical support for transgender people has made fertility preservation strategies possible. Fertility preservation in transgender women mainly relies on sperm cryopreservation. There are few studies on this subject, and the sample sizes are small, and so it difficult to know whether fertility preservation procedures are feasible and effective in trans women. DESIGN: This retrospective study reports the management of fertility preservation in transgender women referred to the study centre for sperm cryopreservation, and the semen parameters of trans women were compared with those of sperm donors. RESULTS: Ninety-six per cent of transgender women who had not started treatment benefitted from sperm cryopreservation, compared with 80% of those who attempted a therapeutic window and 50% of those receiving hormonal treatment at the time of sperm collection. No major impairment of semen parameters was observed in transgender women who had not started GAHT compared with sperm donors. However, even though the frequency of oligozoospermia was no different, two transgender women presented azoospermia. Some transgender women who had started GAHT could benefit from sperm freezing. None of them were treated with gonadotrophin-releasing hormone (GnRH) analogues. CONCLUSIONS: Parenthood strategies for transgender people have long been ignored, but this is an important issue to consider, especially because medical treatments and surgeries may be undertaken in adolescents or very young adults. Fertility preservation should ideally be offered prior to initiation of GAHT.

Fertility preservation in young men with Klinefelter syndrome: A systematic review.

BACKGROUND: Klinefelter syndrome (KS) is the most common cause of genetic male infertility, as most patients present azoospermia. In the testis, a massive decrease in the number of germinal cells is observed and this can begin early in childhood. Thus, it is possible to collect spermatozoa after sperm collection or thanks to testicular sperm extraction (TESE), but the chances finding spermatozoa are decreasing with the age. Sperm collection or TESE should be performed as early as possible. When KS is diagnosed during childhood or teens, fertility preservation could be beneficial. The minimal age for proposing fertility preservation remains controversial and there is no current recommendation about fertility preservation in young men with KS. DESIGN: In this context, we have conducted a systematic review of the results of fertility preservation in young patients with KS to discuss the optimal age range for offering fertility preservation, including or not a TESE. RESULTS: Six articles were included in the systematic review, with patients between 13 and 24 years-old. Except for one, all young men agreed for sperm collection following masturbation. Azoospermia was diagnosed in all patients presenting homogenous KS. One study reported the presence of spermatozoa in the ejaculate of a young man with mosaic KS. Fifty-eight young man for whom ejaculated sperm collection was unsuccessful have benefited from TESE. Testicular spermatozoa were found and frozen in 27 patients out of the 58 (46.5%). The chances of freezing viable testicular sperm between 14 and 23 years of age do not appear to depend on age. CONCLUSION: Fertility preservation should be proposed in young men, but the optimal age for proposing the first sperm collection could be adapted according to the medical context and the psychological maturity of the young man.

Is There an Association of Being Breastfed as an Infant and Fertility Status as an Adult?

Background: Breastfeeding has many short-term and long-term health benefits for infants. Short-term benefits include protection against childhood infections and mortality in low-income countries. The adult long-term effects usually emphasized are a reduction of excess weight and type 2 diabetes. However, there is a lack of available data on the impact of having been breastfed on adult fertility. Indeed, infertility probably has a multifactorial origin, including an environmental origin. The aim of this study was to investigate whether having been breastfed could be associated with unexplained infertility. Materials and Methods: This research is an ancillary study of the case-control study ALIFERT, for which both fertile and infertile couples were recruited. Breastfeeding statuses, collected from childhood health records, were compared among fertile and infertile individuals. Anthropometrics parameters were also used for analysis. Results: About 65.6% of infertile women and 63.3% of fertile women were breastfed, and 69% of infertile men and 67.4% of fertile men were breastfed. There was no statistically significant difference between fertile and infertile groups. Nevertheless, infertile women who were not breastfed had a significantly higher body mass index than those who were breastfed (25.8 kg/m2 vs. 23.2 kg/m2). Conclusion: In our study, we did not observe any association between having been breastfed and fertility in adulthood. However, we observed that, in infertile women, having not been breastfed may influence weight in adulthood. Trial registration: NCT01093378 ALIFERT. Registered: March 25, 2010.

Impact of sleep on female and male reproductive functions: a systematic review.

OBJECTIVE: To evaluate the association of sleep parameters on female and male reproductive functions. DESIGN: Systematic review. SETTING: Not applicable. PATIENT(S): Female and male individuals, either healthy or infertile. INTERVENTION(S): Relevant articles were identified according to the The Preferred Reporting Items for Systematic Reviews and Meta-analyses recommendations in the PubMed and EMBASE databases from January 1, 2000 to June 8, 2020. MAIN OUTCOME MEASURE(S): The association between sleep and ovary function, spermatic function, natural fertility, and in vitro fertilization (IVF) outcomes was assessed. RESULT(S): A total of 33 studies that looked at the association between sleep and either ovary function (n = 10), spermatic function (n = 12), natural fertility (n = 5), or IVF outcomes (n = 6) were included. Overall, female and male fertility, as well as IVF outcomes may be affected by short sleep duration, evening chronotype, or shift/night work schedules. However, the results were hardly comparable due to the heterogeneous study methodologies used. CONCLUSION(S): Sleep may be an original and innovative parameter to consider in the reproduction field. Further investigation is needed to elucidate how sleep and fertility are interrelated and how sleep might constitute a useful modifiable target in infertility management.