[The urologist's role in assisted reproductive technology (ART)]. / Place de l'urologue dans le parcours d'aide médicale à la procréation (AMP).

BACKGROUND: Following on from the Rapport vers une stratégie nationale de lutte contre l'infertilité (Report on a national strategy to combat infertility) submitted to the French Minister of Health in 2022, whose objective 13 is: to better identify and diagnose male infertility, we wanted to clarify with reproductive specialists what role the urologist should play in the management of the infertile couple. METHODS: An expert consensus was reached with the Pedagogical Committee and pilots of the Transversal Specialized Training in Reproductive Medicine and Biology - Andrology, and with the presidents, board and scientific council of the French Federation for Reproductive Study (FFER). RESULTS: In the case of infertility in a couple, the fertility of both partners should be assessed from the outset, and in the event of abnormality or failure of ART, the patient should be referred to a uro-andrologist for expert management. The uro-andrologist will set up medical or surgical treatments to improve the prognosis of the man's fertility, in conjunction with the entire ART team. It is also important for the urologist/andrologist to take charge of the man's health before conception, because of the benefits for the patient himself and for his offspring. CONCLUSION: This expert consensus has shed light on the role of the uro-andrologist in the ART pathway, on the need for training in Andrology and on the medical demography required.

Live birth after intrauterine insemination: is there an upper cut-off for the number of motile spermatozoa inseminated?

RESEARCH QUESTION: To date, most studies have investigated the minimum number of spermatozoa available for intrauterine insemination (IUI), with no data on the maximum number of motile spermatozoa inseminated (NMSI) having been published. This study aimed to determine whether an upper cut-off for the NMSI during IUI exists above which the live birth rate (LBR) is negatively affected. DESIGN: Retrospective analysis of autologous IUI cycles performed between January 2010 and July 2018 in women <43 years old with a NMSI >1 million. The main outcome was the LBR per IUI cycle as a function of the NMSI. RESULTS: A total of 2592 IUI cycles performed in 1017 couples were included. The LBR increased with NMSI up to 30 million without any upper threshold (AUC = 0.5441). The LBR per IUI cycle were 14.5%, 17.9% and 22.7% for NMSI of >1 to ≤10, >10 to ≤20 and >20 to ≤30 million, respectively (P = 0.003). By univariate analysis, the NMSI, female age, number of mature follicles and oestradiol concentrations on day of ovulation triggering, cycle number and infertility aetiology influenced the LBR. Multivariate analysis showed that the LBR was 1.49 and 1.78 times higher when IUI was performed with a NMSI >10 to ≤20 million (odds ratio [OR] 1.49; 95% confidence interval [CI] 1.10-2.02]) and >20 to ≤30 million (OR 1.78; 95% CI 1.08-2.94), respectively, compared with IUI with a NMSI >1 to ≤10 million. CONCLUSIONS: The LBR after IUI can be optimized by inseminating a maximum of motile spermatozoa up to 30 million. Thus, in this specific cohort, IUI preparations should not be diluted when more than 10 million motile spermatozoa are obtained.

Mutation dependance of the mitochondrial DNA copy number in the first stages of human embryogenesis.

Mitochondrial DNA (mtDNA) content is thought to remain stable over the preimplantation period of human embryogenesis that is, therefore, suggested to be entirely dependent on ooplasm mtDNA capital. We have explored the impact of two disease-causing mutations [m.3243A>G myopathy, encephalopathy, lactic acidosis and stroke-like syndrome (MELAS) and m.8344A>G myoclonic epilepsy associated with ragged-red fibers (MERRF)] on mtDNA amounts in human oocytes and day 4-5 preimplantation embryos. The mtDNA amount was stable in MERRF and control materials, whereas gradually increasing from the germinal vesicle of oogenesis to the blastocyst stage of embryogenesis in MELAS cells, MELAS embryos carrying ∼3-fold higher mtDNA amount than control embryos (P = 0.0003). A correlation between mtDNA copy numbers and mutant loads was observed in MELAS embryos (R(2) = 0.42, P < 0.0013), suggestive of a compensation for the respiratory chain defect resulting from high mutation levels. These results suggest that mtDNA can replicate in early embryos and emphasize the need for sufficient amount of wild-type mtDNA to sustain embryonic development in humans.

Poor correlations in the levels of pathogenic mitochondrial DNA mutations in polar bodies versus oocytes and blastomeres in humans.

Because the mtDNA amount remains stable in the early embryo until uterine implantation, early human development is completely dependent on the mtDNA pool of the mature oocyte. Both quantitative and qualitative mtDNA defects therefore may negatively impact oocyte competence or early embryonic development. However, nothing is known about segregation of mutant and wild-type mtDNA molecules during human meiosis. To investigate this point, we compared the mutant levels in 51 first polar bodies (PBs) and their counterpart (oocytes, blastomeres, or whole embryos), at risk of having (1) the "MELAS" m.3243A>G mutation in MT-TL1 (n = 30), (2) the "MERRF" m.8344A>G mutation in MT-TK (n = 15), and (3) the m.9185T>G mutation located in MT-ATP6 (n = 6). Seven out of 51 of the PBs were mutation free and had homoplasmic wild-type counterparts. In the heteroplasmic PBs, measurement of the mutant load was a rough estimate of the counterpart mutation level (R(2) = 0.52), and high mutant-load differentials between the two populations were occasionally observed (ranging from -34% to +34%). The mutant-load differentials between the PB and its counterpart were higher in highly mutated PBs, suggestive of a selection process acting against highly mutated cells during gametogenesis or early embryonic development. Finally, individual discrepancies in mutant loads between PBs and their counterparts make PB-based preconception diagnosis unreliable for the prevention of mtDNA disorder transmission. Such differences were not observed in animal models, and they emphasize the need to conduct thorough studies on mtDNA segregation in humans.

[Menometrorrhagia]. / Une prise en charge qui répond à un algorithme précis. Ménométrorragies.

Menometrorrhagia is a frequent cause of medical consulting. After exclusion of pregnancy, main aetiologies are the uterine (polyp, myoma, adenomyosis, cancer) or adnexial abnormality (ovarian cyst or cancer), the disorders of hemostasis (Willebrand...), the dysfunctional uterine bleeding. A clinical examination is necessary to provide an accurate diagnosis and find complications such as anaemia. Pelvic ultrasound examination and endometrial biopsy are required to eliminate endometrial cancer. The treatment of menometrorrhagia consists of symptomatic treatment (tranexamic acid, levonorgestrel intrauterine device) and specific treatment of its cause (hysteroscopic resection of myom, polyp, endometrectomy, hysterectomy).

[Extending preimplantation genetic diagnosis to HLA typing: the French exception]. / Le diagnostic pré-implantatoire couplé au typage HLA: l'expérience française.

Umut-Talha, a "sibling savior", was born on 26 January 2011 at Beclère Hospital after embryo selection at the Paris preimplantation genetic diagnosis (PGD) center. His birth revived the controversy over "double PGD". This procedure, authorized in France since 2006, allows couples who already have a child with a serious, incurable genetic disease, to opt for PGD in order to select a healthy embryo that is HLA-matched to the affected sibling and who may thus serve as an ombilical cord blood donor. The procedure is particularly complex and the baby take-home rate is still very low. Double PGD is strictly regulated in France, and candidate couples must first receive individual authorization from the Biomedicine Agency. In our experience, these couples have a strong desire to have children, as reflected by the large number of prior spontaneous pregnancies (25% of couples). Likewise, most of these couples request embryo transfer even when there is no HLA-matched embryo, which accounts for more than half of embryo transfers. The controversy surrounding this practice has flared up again in recent weeks, over the concepts of "designer babies" and "double savior siblings" (the baby is selected to be free of the hereditary disease, and may also serve as a stem cell donor for the affected sibling).

[Ten years' experience of preimplantation genetic diagnosis in Paris: remaining obstacles and potential solutions]. / Diagnostic pré-implantatoire: dix ans d'expérience en région parisienne: impasse actuelle et solutions à venir.

Preimplantation genetic diagnosis (PGD) has been authorized in France since 1999. Encouraging results have been obtained during the past 10 years in our Paris center, where 832 patients have undergone 1056 IVF-PGD procedures. With the advent of new techniques for the identification of genetic disease markers, our center can now offer PGD procedures for aneuploidy and 75 single-gene diseases. New indications for PGD have also been developed, such as mitochondrial DNA diseases, amyloid neuropathy, pulmonary arterial hypertension, and HLA typing The implantation rate is currently 29,6% and, by 31 December 2009, 151 healthy babies had been born. Unfortunately, demand for PGD procedures far outstrips available technical capacity, and the waiting period is longer than 18 months. Increased funding is urgently needed

Evaluation of SARS-CoV-2 in semen, seminal plasma, and spermatozoa pellet of COVID-19 patients in the acute stage of infection.

To date, there is limited information about the presence of SARS-CoV-2 in semen especially in the acute phase of the infection. While available data from cohort studies including a total of 342 patients in the acute or recovery phase of the infection are reassuring, one study mentioned detecting virus in the semen of 6/38 COVID-19 patients. Here we assessed SARS-CoV-2 presence in the semen of COVID-19 positive patients in the acute stage of infection, within 24 hours of the positive nasopharyngeal swabs. Semen, seminal plasma and spermatozoa pellet were screened for SARS-CoV-2 and manual or airborne contamination during semen sampling. Among the 32 COVID-19 volunteers, the median interval from the onset of symptoms to semen collection was 4 days [IQR: 0-8]. Only one presented positive SARS-CoV-2 PCR in semen and seminal plasma fractions, although the spermatozoa pellet was negative. Viral cultures were all negative. We observed slightly higher concentrations of bacterial DNA in the SARS-CoV-2 positive specimen than in all negative samples. The bacteria identified neither confirm nor rule out contamination by oropharyngeal secretions during collection. SARS-CoV-2 was rarely present in semen during the acute phase of the disease. This very rare situation could be connected to oral or manual contamination during semen collection. The possible presence of SARS-CoV-2 in semen calls for nasopharyngeal viral testing and strict hygiene protocols during semen collection before assisted reproductive attempts.

Students' views on the impact of two pedagogical tools for the teaching of breast and pelvic examination techniques (video-clip and training model): a comparative study.

OBJECTIVE: To investigate and compare the views and experience of undergraduate medical students concerning two methods used in the teaching of pelvic and breast examinations: a video clip and a training model. STUDY DESIGN: Following the teaching sessions, the students (n=79; female 67%; median age 20; students' grade level: 2nd study year (87%) and 3rd study year (13%)) completed a satisfaction questionnaire, which included items related to the pedagogical value of these two different types of tool. RESULTS: Most of the students ranked their own satisfaction in each teaching session as either very satisfied or satisfied: the median rating was 3 or 4 for each item. For their satisfaction with the pedagogical tools, in terms of the degree to which they contributed toward practical knowledge of the examination procedures, the students rated the video clip with a higher degree of satisfaction than the training model, for both breast (very satisfied 73% vs. 40%, satisfied 27% vs. 43%, unsatisfied 0% vs. 7% (P<0.001)) and pelvic examinations (very satisfied 57% vs. 33%, satisfied 39% vs. 66%, unsatisfied 4% vs. 1% (P<0.004), respectively. CONCLUSION: Teaching sessions for pelvic and breast examination, which make combined use of videos and training models, are associated with a high degree of satisfaction from students in their 2nd or 3rd student's year.

Reliability of automated volumetric measurement of multiple growing follicles in controlled ovarian hyperstimulation.

OBJECTIVE: To evaluate the reliability of a computer-assisted approach for automatically measuring ovarian follicles during controlled ovarian hyperstimulation (COH). DESIGN: Prospective, comparative study. SETTING: Hospital Béclère, Clamart, France. PATIENT(S): Twenty-seven infertile IVF-ET candidates undergoing COH. INTERVENTION(S): Just before the oocyte retrieval, growing follicles (n=72) had their mean diameters measured and their volumes determined semimanually by virtual organ computer-aided analysis (VOCAL) and automatically by SonoAVC. Follicles were sorted in small (12-16 mm; n=35) and large (>16 mm; n=37) growing follicles. Measures were compared with the follicular fluid volume. MAIN OUTCOME MEASURE(S): Concordance of results using intraclass correlation coefficient and limits of agreement methods, respectively. RESULT(S): Overall, VOCAL (median: 3.42 mL; range: 0.98-9.68 mL) and SonoAVC (3.25 mL; 0.98-8.63 mL) measurements were equivalent to the corresponding actual follicle volume (3.20 mL; 0.80-10.20 mL). The intraclass correlation coefficient values between follicular fluid volume and mean diameter, VOCAL, and SonoAVC were 0.51, 0.95, and 0.98, respectively, for small follicles, and 0.80, 0.93, and 0.92, respectively, for large follicles. 95% limits of agreement between actual volume and VOCAL (-1.09 to +1.07 mL) and SonoAVC (-1.08 to +0.84 mL) measurements were comparable in both groups. CONCLUSION(S): Automated measurement of multiple follicular volumes using SonoAVC is a simple technique, which reliability is superior to usual diameter measurements and comparable to VOCAL. This technologic refinement invites us to switch toward volumetric monitoring of follicle growth during COH.

Reproducibility and reliability of automated volumetric measurement of single preovulatory follicles using SonoAVC.

OBJECTIVE: To evaluate the reproducibility and the reliability of an innovative, computer-assisted approach for automatically measuring ovarian follicles. DESIGN: Prospective, comparative study. SETTING: Hospital Béclère, Clamart, France. PATIENT(S): Fifteen infertile women undergoing IVF-ET in monodominant follicle cycles. INTERVENTION(S): Just before oocyte retrieval, follicles were three-dimensionally reconstructed from transvaginal ultrasonographic images. Volumes were determined both manually by visual outlining of inner follicle borders (VOCAL) and automatically using SonoAVC. Each procedure was repeated three times. Follicular fluid volume indicated the actual follicle volume. MAIN OUTCOME MEASURE(S): Reproducibility and concordance of results were assessed by the intraclass correlation coefficient (ICC) and the limits of agreement method, respectively. RESULT(S): At any time, VOCAL (3.68, 2.41-8.29 mL; 3.73, 2.70-7.16 mL; 3.89, 2.96-7.83 mL; median, ranges, respectively) and SonoAVC (3.57, 2.41-8.19 mL; 3.71, 2.49-8.90 mL; 4.07, 3.12-8.16 mL, respectively) volume measurements failed to be statistically different from the corresponding actual follicle volume (3.60, 2.90-8.00 mL). Reproducibility (ICC, 95% confidence intervals) of repeated VOCAL (0.95, 0.87-0.98) and SonoAVC (0.97, 0.94-0.99) measurements as well as 95% limits of agreement between actual volumes and VOCAL (-0.48 to +0.80 mL) and SonoAVC (-0.61 to +0.99 mL) measurements were comparable. CONCLUSION(S): Automatic measurement of ovarian follicle volumes from three-dimensionally reconstructed ultrasound images (SonoAVC) is a rapid and simple technique, which reproducibility and reliability are comparable to the semimanual technique (VOCAL). It opens new perspectives for the accurate and objective assessment of ovarian function by ultrasound.