Centre for Medically Assisted Procreation

BackgroundPolycystic ovary syndrome (PCOS) and obesity can both disrupt reproductive function. However, the extent to which obesity contributes to PCOS manifestations is not very clear. This study aimed to disentangle the relative contributions of PCOS and obesity for reproductive dysfunction in women undergoing in vitro fertilization (IVF).MethodsA total of 129 women undergoing IVF treatments were recruited. Women were allocated into four groups according to body mass index (BMI) and PCOS diagnosis: normal-weight controls (n = 33; 21.70 ± 1.85 kg/m²), overweight/obesity controls (n = 28; 28.35 ± 3.05 kg/m²), normal-weight PCOS (n = 31; 21.92 ± 1.95 kg/m²), and overweight/obesity PCOS (n = 37; 31.67 ± 5.03 kg/m²). Circulating levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), glucose and insulin were measured in all groups, while insulin resistance was assessed by the Homeostatic Model (HOMA-IR). Additionally, on the oocyte retrieval day, ∆4-androstenedione, testosterone, progesterone and sex hormone-binding globulin (SHBG), were measured in plasma and follicular fluid (FF). IVF outcomes evaluated included the number of oocytes retrieved, oocyte immaturity, as well as fertilization and blastocyst formation rates. A multivariate analysis was performed to determine the independent effects of PCOS and obesity for reproductive and metabolic parameters.ResultsWomen with PCOS presented significantly higher AMH levels, LH: FSH ratio, and lower FF progesterone levels, confirming these as PCOS-specific signatures regardless of BMI. In contrast, women with overweight/obesity had lower plasma and FF SHBG levels and greater HOMA-IR, independently of PCOS. Furthermore, ∆4-androstenedione and testosterone levels in plasma and FF were significantly higher in women with PCOS and overweight/obesity as compared to normal-weight women with PCOS. Despite the higher oocyte retrieval rates in women with PCOS, no differences in oocyte immaturity, fertilization and blastocyst formation rates were observed.ConclusionsPCOS and obesity independently disrupt female reproductive function suggesting that features associated with each condition may differ. Furthermore, our study shows that obesity exacerbates hyperandrogenism in women with PCOS, highlighting a synergistic detrimental impact on female reproductive function.

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ObjectiveTo update the 2010 CNGOF clinical practice guidelines for the first-line management of infertile couples. Materials and methodsFive 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. ResultsThe 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. ConclusionBased on strong agreement between experts, we have been able to formulate updated recommendations in 28 areas concerning the initial management of infertile couples.

Male infertility is common and complex, presenting a wide range of heterogeneous phenotypes. Although about 50% of cases are estimated to have a genetic component, the underlying cause often remains undetermined. Here, from whole-exome sequencing on samples from 168 infertile men with asthenoteratozoospermia due to severe sperm flagellum, we identified homozygous ZMYND12 variants in four unrelated patients. In sperm cells from these individuals, immunofluorescence revealed altered localization of DNAH1, DNALI1, WDR66 and TTC29. Axonemal localization of ZMYND12 ortholog TbTAX-1 was confirmed using the Trypanosoma brucei model. RNAi knock-down of TbTAX-1 dramatically affected flagellar motility, with a phenotype similar to the sperm from men bearing homozygous ZMYND12 variants. Co-immunoprecipitation and ultrastructure expansion microscopy in T. brucei revealed TbTAX-1 to form a complex with TTC29. Comparative proteomics with samples from Trypanosoma and Ttc29 KO mice identified a third member of this complex: DNAH1. The data presented revealed that ZMYND12 is part of the same axonemal complex as TTC29 and DNAH1, which is critical for flagellum function and assembly in humans, and Trypanosoma. ZMYND12 is thus a new asthenoteratozoospermia-associated gene, bi-allelic variants of which cause severe flagellum malformations and primary male infertility.

The aim of the study is to rethink the ethics of advanced motherhood. In the literature, delayed childbearing is usually discussed in the context of reproductive justice, and in relationship to ethical issues associated with the use and risk of assisted reproductive technologies. We aim to go beyond these more “traditional” ways in which reproductive ethics is framed by revisiting ethics itself through the lens of the figure of the so-called “older” mother. For this purpose, we start by exploring some of the deep seated socio-cultural discourses in the context of procreation: ageism, ableism and the widespread bias towards geneticism and pronatalism. Afterwards, we provide a critical overview of the key arguments against or in support of advanced motherhood. We then briefly discuss how entrenchment by both sides has produced an impasse in the debate on the ethics of advanced motherhood and proceed by arguing that it is fundamental to bring about a change in this narrative. For this purpose, we will revisit the feminist usage of the concept of vulnerability which will allow us both to criticize culturally prescribed norms about motherhood and to address the painful reality of age-related fertility decline. In the last section, we argue that instead of defining “older” motherhood as an ethical problem, we should problematize the fact that female reproductive ageing is an understudied and ill-sourced topic. We believe that allocating resources to research to better understand female reproductive ageing is not only ethically permissible, but might even be ethically desirable.

Turner syndrome association with multi-organ system comorbidities highlights the need for effective implementation of follow-up guidelines. We aimed to assess the adequacy of care with international guidelines published in 2007 and 2017 and to describe the phenotype of patients. In this multicenter retrospective descriptive cohort study, we collected growth and pubertal parameters, associated comorbidities, treatment, and karyotype in patients diagnosed at age <18 years between 1993 and 2022. We assessed age-appropriate recommendation follow-up (children, adolescents and adults) according to the 2007 guidelines if the last visit was before 2017 (18 recommendations) and the 2017 guidelines if the last visit was after 2017 (19 recommendations). We included 68 patients followed at Lausanne University Hospital (n=64) and at Neuchatel Regional Hospital (RHNe) (n=4). 2.9% of patients underwent all recommended investigations.Overall, 68.9 ± 22.5% and 78.5 ± 20.6% of the recommendations were followed, before and after 2017 respectively. High implementation rates were found for height, weight and BMI (100%), cardiac (80 to 100%) and renal (90 to 100%) imaging. Low implementation rates were found for Ear, Nose and Throat (ENT) (56.5%), skin (38.5%), dental (23.1%), ophthalmological (10%) and cholestasis (0 to 29%) assessments, depending on age and time of visit. In adults (n=33), the mean proportion of followed recommendations was lower before than after 2017: 63.5 ± 25.8% vs. 78.7 ± 23.4%, p=0.039. Growth parameters, cardiac and renal imaging are well followed. However, efforts should be made for dental, ENT, ophthalmological, skin and cholestasis assessments. Adequacy of follow-up improved with the quality of transition to adult care.

The acceptance of "marriage for all" in Switzerland has enabled married couples to have access to medically assisted reproduction (MAR) through sperm donation from July 2022. We present the Swiss legal context of sperm donation, the different techniques, the selection of donors and the method of attribution to recipient couples. This article also describes the complexities of managing a sperm bank in Switzerland, presents some of the figures associated and address the fundamental question of access to origins and the secrecy that may be linked to sperm donation.

Ouverture de la PMA aux couples de femmes : une (r)évolution qui s'imposeAlors que le projet de mariage pour tous et toutes semble sur le point d'être accepté par les Chambres fédérales, la question de l'accès à la procréation médicalement assistée (PMA) pour les couples de femmes est, quant à elle, beaucoup plus controversée.Dans cette contribution, l'auteure examine dans quelle mesure l'exclusion des couples de femmes des techniques de procréation médicalement assistée est conforme au principe de non-discrimination consacré par la CEDH.