[Assessment of the man in the infertile couple]. / Évaluation de l'homme du couple infertile.

BACKGROUND: Among couples consulting for infertility, there is a male component, either alone or associated with a female aetiology in around one in 2 cases. MATERIAL AND METHODS: Bibliographic search in PubMed using the keywords "male infertility", "diagnosis", "management" and "evaluation" limited to clinical articles in English and French prior to 1/01/2023. RESULTS: The AFU recommends: (1) a complete medical history including: family history, patient history affecting fertility, lifestyle habits (toxicity), treatments, symptoms, sexual dysfunctions; (2) a physical examination including: BMI, signs of hypogonadism, secondary sexual characteristics, scrotal examination (volume and consistency of testes, vas deferens, epididymal or testicular nodules, presence of varicocele); (3) two spermograms, if abnormal on the first; (4) a systematic scrotal ultrasound,± an endorectal ultrasound depending on the clinic; (5) a hormonal work-up (testosterone, FSH; if testosterone is low: LH assay to differentiate between central or peripheral hypogonadism); (6) karyotype if sperm concentration≤10 million/mL; (7) evaluation of Y chromosome microdeletions if concentration≤1 million/mL; (8) evaluation of the CFTR gene in cases of suspected bilateral or unilateral agenesis of the vas deferens and seminal vesicles. The role and usefulness of direct and indirect tests to assess the effects of oxidative stress on sperm DNA will also be explained. CONCLUSION: This review complements and updates the AFU/SALF 2021 recommendations.

COVID-19 infection in first trimester of pregnancy marked by a liver cytolysis in a woman previously treated by hydroxychloroquine for repeated implantation failure: a case report.

BACKGROUND: In December 2019, a new disease (COVID-19) caused by a novel coronavirus called SARS-CoV-2 emerged in China and spread to many other countries. There is only limited data about the clinical features of COVID-19 during pregnancy, especially in first trimester. CASE PRESENTATION: We report a COVID-19 infection in a 35 years-old patient in first trimester of pregnancy and its consequent medical care. At 7 weeks of pregnancy, the patient, who did not have any pregestational comorbidities, complained of intense nausea and asthenia. An important liver cytolysis was discovered with biological perturbations of transaminases levels. No respiratory symptoms were recorded. Classical viral aetiologies and drug-related toxicity were discarded. Because of the aggravation of the symptoms and the occurrence of the breathlessness, the patient was tested for the COVID-19 in a nasopharyngeal swab. The RTq-PCR assay indicated the presence of SARS-CoV-2 RNA. In the absence of severe symptoms, the patient was monitored at home according to the French government guidelines. After a few days, the symptoms resolved without any complications. The pregnancy is still ongoing without any visible sequelae on the foetus so far. CONCLUSIONS: This first case illustrated the difficulty of COVID-19 diagnosis in patients with isolated digestive symptoms in first trimester of pregnancy that could be confused with gravida hyperemesis. Monitoring of pregnancy after an episode of COVID-19 should be strengthened with bimonthly foetal growth ultrasounds and doppler assessments because of the risks for intrauterine growth restriction. Comprehensive data on larger numbers of first trimester gravid women with COVID-19 are required to better understanding the overall impact of SARS-CoV-2 on maternal and birth outcomes.

Embryotoxicity testing of IVF disposables: how do manufacturers test?

STUDY QUESTION: How do manufacturers perform embryotoxicity testing in their quality control programs when validating IVF consumables? SUMMARY ANSWER: The Mouse Embryo Assay (MEA) and Human Sperm Survival Assay (HSSA) used for IVF disposables differed from one manufacturer to another. WHAT IS KNOWN ALREADY: Many components used in IVF laboratories, such as culture media and disposable consumables, may negatively impact human embryonic development. STUDY DESIGN, SIZE, DURATION: Through a questionnaire-based survey, the main manufacturers of IVF disposable devices were contacted during the period November to December 2018 to compare the methodology of the MEA and HSSA. We focused on catheters for embryo transfer, catheters for insemination, straws, serological pipettes, culture dishes and puncture needles used in the ART procedures. PARTICIPANTS/MATERIALS, SETTING, METHODS: We approached the manufacturers of IVF disposables and asked for details about methodology of the MEA and HSSA performed for toxicity testing of their IVF disposable devices. All specific parameters like mouse strains, number of embryos used, culture conditions (media, temperature, atmosphere), extraction protocol, subcontracting, and thresholds were registered and compared between companies. MAIN RESULTS AND THE ROLE OF CHANCE: Twenty-one companies were approached, of which only 11 answered the questionnaire. Significant differences existed in the methodologies and thresholds of the MEA and HSSA used for toxicity testing of IVF disposables. Importantly, some of these parameters could influence the sensitivity of the tests. LIMITATIONS, REASONS FOR CAUTION: Although we approached the main IVF manufacturers, the response rate was relatively low. WIDER IMPLICATIONS OF THE FINDINGS: Our study confirms the high degree of heterogeneity of the embryotoxicity tests performed by manufacturers when validating their IVF disposable devices. Currently, no regulations exist on this issue. Professionals should call for and request standardization and a future higher degree of transparency as regards embryotoxicity testing from supplying companies; moreover, companies should be urged to provide the users clear and precise information about the results of their tests and how testing was performed. Future recommendations are urgently awaited to improve the sensitivity and reproducibility of embryotoxicity assays over time. STUDY FUNDING/COMPETING INTEREST(S): This study did not receive any funding. L.D. declares a competing interest with Patrick Choay SAS. TRIAL REGISTRATION NUMBER: N/A.

[Polycystic ovary syndrome does not affect blastulation nor cumulative live birth rates]. / Le syndrome des ovaires polykystiques n'altère pas les taux de blastulation ni les taux cumulés de naissances vivantes.

OBJECTIVES: Polycystic ovarian syndrome (PCOS) brings complications in the management of the assisted reproductive technology (ART) because of an oocyte quality probably impaired due to modifications of intra- and extra-ovarian factors. Our study aimed to investigate the extended culture in PCOS patients and its influence on the cumulative live birth rates. METHODS: Fifty-nine PCOS patients (as defined by the Rotterdam criteria) and 114 normo-ovulatory patients (i.e. with tubal, male or idiopathic infertility, regular cycles and AMH>2ng/mL) aged<37years old who underwent a 1st or 2nd ART attempt with extended culture to day 6 were included from October 2015 to December 2017. The blastulation and cumulative live birth rates were compared between the two groups. RESULTS: The PCOS and control patients were 32.22 and 32.91years old respectively (P=0.05). The median number of oocytes retrieved was significantly higher in the PCOS group and the median oocyte maturity rate significantly lower compared with controls. The blastulation rates were similar between the PCOS and the control groups, respectively 57.8% vs. 58.6%, P=0.88. Because of the risks of hyperstimulation syndrome, a freeze all strategy was achieved for 38.9% of PCOS patients vs. 14.0% of the control patients (P<0.01). The cumulative live birth rates were not statistically different: 31.7% in the PCOS group vs. 37.2% in the control group, P=0.50. CONCLUSIONS: PCOS was not observed to affect the extended culture nor the cumulative live birth rates in comparison to normo-ovulatory patients, supporting the blastocyst transfer strategy as a suitable option to PCOS patients.

[Intra-uterine insemination outcomes according to the serum AMH level on day 3]. / Valeur prédictive de l'hormone antimüllérienne sur les issues des inséminations intra-utérines.

UNLABELLED: The aim of this retrospective study was to compare the IUI outcomes according to serum antiMullerian hormone (AMH) levels on day 3 of cycle. PATIENTS AND METHOD: Three hundred and sixteen patients undergoing their first IUI cycle after a serum AMH level test in our laboratory. These patients were less than 39 years of age and the number of motile spermatozoa inseminated (NMSI) was superior or equal to five millions. Patients were divided in three groups according to their serum AMH level: the group 1 with AMH level less than 1ng/ml, the group 2 with AMH level between 1 and 4.5ng/ml, and the group 3 with AMH level greater than 4.5ng/ml. MAIN OUTCOMES MEASURE(S): clinical pregnancy rate and ongoing pregnancy rate per IUI cycle. RESULT(S): No statistical difference has been observed on follicle stimulation, number of mature follicle, oestradiol level on day hCG, clinical pregnancy rate, spontaneous abortion. The ongoing pregnancy rate per IUI practised were respectively: 15.5% for AMH inferior to 1ng/ml versus 15.2% for AMH between 1 to 4.5ng/ml and versus 13.6% for AMH superior to 4.5ng/ml. CONCLUSION(S): AMH value does not seem to have an impact on the IUI outcomes and particularly on the pregnancy rates.

[Cancellation of IVF-ET cycles: poor prognosis, poor responder, or variability of the response to controlled ovarian hyperstimulation? An analysis of 142 cancellations]. / Annulations en fécondation in vitro : mauvais pronostic, mauvaises répondeuses, ou variabilité de la réponse à la stimulation ? Analyse de 142 annulations.

INTRODUCTION: This retrospective study aimed at analyzing IVF-ET management and outcome after cancellation of a first cycle for poor response. PATIENTS AND METHOD: One hundred and forty-two infertile patients were included in this observational study. After an overall analysis on the outcome of the second IVF-ET attempt, a sub-analysis was performed according to the presence or the absence of poor prognostic criteria defined as mentioned: patient age superior to 38 years old, antral follicle count (3-9 mm in diameter) inferior to 10 on cycle day 3 and day 3 serum AMH and FSH levels less than 1 ng/mL and more than 10 IU/mL, respectively. Main outcome measures were the cancellation rates, pregnancy and live birth rates. RESULTS: When a controlled ovarian stimulation was performed, patients with poor prognosis had higher cancellation rates (37.8% vs. 13.3%, P<0.004) and lower pregnancy and live birth rates (22.2% vs. 35.0%, P<0.05 and 11.1% vs. 26.1%, P<0.05, respectively) as compared to good prognosis women. CONCLUSION: The relatively high cancellation rate in patients with poor prognosis raises the question of the use of IVF modified natural cycle in this group.

[Are mild ovarian stimulations for IVF-ET a significant progress in assisted reproductive technologies?]. / Les stimulations ovariennes modérées pour fécondation in vitro constituent-elles un réel progrès en assistance médicale à la procréation ?

Growing evidence indicates that mild ovarian stimulation for in vitro-fertilization-embryo transfer may be an interesting approach to reduce the incidence and severity of complications, the number of treatment days, cost, patient discomfort and number of patient drop-outs. However, the heterogeneity of FSH-sensitive follicles, presumably requires multiple follicular growth to improve oocyte-embryo selection. In addition, whether the acceptability probably is similar between standard ovarian stimulation and mild stimulation, per-treatment pregnancy rates with conventional stimulation is superior to mild stimulation in unselected populations. Hence, some specific indications tend to emerge such as alterations of the ovarian follicular reserve in women of less than 38 years, bad embryo qualities and implantation failure after conventional stimulation, patients with previous history of hyperstimulation syndrome or contraindications to hyperoestrogenia (estrogeno-related cancers and thromboembolic diseases). However, no randomized trials have ever been performed to compare the results of mild versus conventional stimulation in young patients and good responders. Therefore, there is insufficient scientific evidence to shift from standard stimulation to mild stimulation for all patients. Cultural standards have to be considered in the choice of the type of stimulation.

[Preimplantation diagnosis with HLA typing: birth of the first double hope child in France]. / Diagnostic préimplantatoire avec typage HLA : naissance du premier enfant du double espoir en France.

Preimplantation genetic diagnosis (PGD) is authorized in France since 1999. After 10 years, technical results are encouraging. With the development of new technologies, our team is able to diagnosis the large majority of chromosome translocations and 75 monogenic diseases. However, PGD remains limited because of the growing augmentation of demands causing an increasing delay for the first procedure of more than 18 months. Since 2006, 19 couples asked for a PGD with HLA typing. In January 2011, 11 couples have already been included in our PGD program. The birth of the first child after PGD with HLA typing offers new perspectives of treatment for these couples.

[Ovarian hyperstimulation syndrome: pathophysiology, risk factors, prevention, diagnosis and treatment]. / Le syndrome d'hyperstimulation ovarienne : physiopathologie, facteurs de risque, prévention et prise en charge.

The ovarian hyperstimulation syndrome is a major complication of ovulation induction for in vitro fertilization, with severe morbidity and possible mortality. Whereas its pathophysiology remains ill-established, the VEGF may play a key role as well as coagulation disturbances. Risk factors for severe OHSS may be related to patients characteristics or to the management of the ovarian stimulation. Two types of OHSS are usually distinguished: the early OHSS, immediately following the ovulation triggering and a later and more severe one, occurring in case of pregnancy. As no etiologic treatment is available, the therapeutic management of OHSS should focus on its related-complications. Thrombotic complications that can occur in venous or arterial vessels represent the major risk of OHSS, possibly conducting to myocardial infarction and cerebrovascular accidents. Once the OHSS is diagnosed, prevention of thrombotic accidents remains the major issue.

[Serum AMH level is not a predictive value for IVF in modified natural cycle: analysis of 342 cycles]. / L'AMH sérique n'a pas de valeur prédictive en fécondation in vitro en cycle naturel modifié : analyse de 342 cycles.

The objective is to compare the IVF procedures in modified natural cycle outcomes according to serum anti-Mullerian hormone (AMH) levels. We included in this retrospective study 342 patients undergoing their first IVF in modified natural cycle. Patients were regrouped in three groups according to their serum AMH level: group 1 was defined by patients with AMH level<0.97 ng/mL (<25th percentile), group 2, patients with AMH level between 0.97 ng/mL and 2.60 ng/mL (25-75th percentile), and group 3, patients with AMH level between 2.61 ng/mL and 6.99 ng/mL (>75th percentile). The main outcomes were cancellation rate, embryo transfer rate and clinical pregnancy rate, ongoing pregnancy rate and implantation rate. No difference has been observed on cancellation rate, embryo transfer rate, clinical pregnancy rate and implantation rate. The ongoing pregnancy rate per IVF cycle was respectively: 12.8±3.6% for AMH inferior to 0.97 ng/mL versus 12.5±2.5% for AMH between 0.97 to 2.60 ng/mL and 13.4±4.2% for AMH between 2.61 ng/mL and 6.99 ng/mL. In conclusion, IVF in modified natural cycles procedures should be considered as an option for patients with an altered ovarian reserve defined by a serum AMH inferior to 1 ng/mL. Serum AMH level seems a quantitative marker of the ovary but not a quality factor. Serum AMH level does not seem to be a prognostic factor for ongoing pregnancy rated in IVF modified cycles.

[Impact of elective single embryo transfer criteria on the twin pregnancy rate in a French population]. / L'impact des critères du élective single embryo transfer sur le taux de grossesses gémellaires dans la population française.

To reduce the twin pregnancy rate and their morbidity, several recommendations have been proposed to practice the "elective single embryo transfer" in a selected population. We decided to apply the criteria that were proposed in five articles from the literature to our population to evaluate the percentage of our population concerned and the impact on our twin pregnancy rate. The result is that these criteria only concern 2,4 to 10,8% of our population with a minor reduction of our twin pregnancy rate with a potential lake of chance concerning the pregnancy rate. We should study others possibilities than the population's criteria to reduce the number of embryo transferred.

[Watch out for headaches at the end of a pregnancy! Do not miss an autoimmune hypositys]. / Attention aux céphalées de fin de grossesse! Ne pas méconnaître une hypophysite.

We report the case of a 21-year-old pregnant women (36 WA) presenting intensive headaches and visual disturbances. Those sellar compression symptoms have made us suppose the diagnosis of autoimmune hypophysitis. MRI has confirmed the typical aspect of symmetric enlargement of the pituitary gland with a strong and homogenous enhancement after gadolinium. This pathology associated to a high morbidity and mortality due to partial or complete deficit of the anterior pituitary hormones, shall be reminded more often.

[The role of ultrasound examination to evaluate ovarian reserve of infertile patients]. / Place de l'échographie pour le bilan de la réserve ovarienne dans le cadre d'une infertilité

The accurate assessment of ovarian reserve is an essential step before the treatment of infertile couples. Ovarian reserve could either be evaluated through clinical or biological parameters, but ultrasound plays a remarkable role, since it permits the direct visualization and count of ovarian antral follicles. Nevertheless, the available literature data are conflicting about the real sensibility and specificity of this method to predict the exact number of retrieved oocytes or the occurrence of pregnancy after a procedure for medical assisted reproduction. New technologies have been developed, as the 3D-ultrasound, who does not ameliorate ultrasound accuracy, but permits the reduction of the time necessary for patient's examination and virtually eliminates inter- and intra-observer bias. The place of the ovarian artery flow evaluation by Doppler remains unclear and need more studies.