[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.

Structural analysis of the impact of a novel androgen receptor gene mutation in two adult patients with mild androgen insensitivity syndrome.

Androgen receptor gene (AR) mutations are responsible for androgen insensitivity syndrome (AIS) presenting with a clinical phenotype that ranges from gynaecomastia and/ or infertility in mild AIS (MAIS) to complete testicular feminisation in complete AIS. We report a novel AR gene mutation in two unrelated adult patients with MAIS and we studied its functional impact using 3D modelling. Patient 1, referred for infertility, presented with gynaecomastia, mild hypospadias and bilateral testicular hypotrophy contrasting with high testosterone levels, an elevated FSH, an elevated androgen sensitivity index (ASI) and oligoasthenoteratospermia. In vitro fertilisation and intracytoplasmic sperm injection resulted in a successful twin pregnancy. Patient 2 referred for a decrease in athletic performance had surgically treated gynaecomastia, oligoasthenospermia, high testosterone levels and an elevated ASI. Despite his impaired spermogram, he fathered two children without assisted reproductive technology. AR gene sequencing in the two patients revealed a common novel missense mutation, Ala699Thr, in exon 4 within the ligand-binding domain. 3D modelling studies showed that this mutation may impact dimer stability upon ligand binding or may affect allosteric changes upon dimerisation. This study illustrates the value of structural analysis for the functional study of mutations and expands the database of AR gene mutations.

Proximal occlusion of hydrosalpinges by Essure(®) before assisted reproduction techniques: a French survey.

OBJECTIVES: To study the feasibility and results (live-birth and complication rates) of placement of Essure(®) microinserts before assisted reproductive technology (ART) treatment of women with hydrosalpinx when laparoscopy should be avoided. Study design National survey of 45 French hospital centres providing ART reporting a retrospective analysis of 43 women with unilateral or bilateral hydrosalpinges and Essure(®) placement. The results of the following ART cycle were studied for 54 embryo transfers. RESULTS: The placement success rate reached 92.8% (65/70 tubes), and the mean number of visible intrauterine coils was 1.61 (range: 0-6). Pyosalpinx occurred in one case, and expulsion of the device into the uterus in two others. Of 43 women, 29 (67.4%) had a total of 54 fresh or frozen embryos transferred. The clinical pregnancy rate was 40.7% (22/54) and the live-birth rate 25.9% (14/54). The implantation rate was 29.3% (27/92). CONCLUSION: Essure(®) placement is an effective method for occlusion of hydrosalpinges before IVF. Monitoring the live-birth rate confirms that this option is the strongest in cases when laparoscopy is impossible or contraindicated.

Cumulative pregnancy rate after ICSI-IVF in patients with colorectal endometriosis: results of a multicentre study.

BACKGROUND: There is currently no consensus about indications for surgery for infertility associated with colorectal endometriosis. The aim of this study was to evaluate cumulative pregnancy rates (CPRs) after ICSI-IVF cycles in patients with colorectal endometriosis and to identify determinant factors of fertility outcome. METHODS: Prospective longitudinal multicentre study from January 2005 to June 2011. We included 75 patients with colorectal endometriosis and proved infertility without prior surgery for deep infiltrating endometriosis. Univariable analysis was used to identify determinant factors of pregnancy rate. CPR was calculated using cumulative-incidence methods from log-rank test and Kaplan-Meier curves. For multivariable analysis, Cox proportional hazards model was used. RESULTS: For CPR per patient analysis, the total number of cycles was 113 and the median number of cycles per patient was 1 (range: 1-3). In the whole population the CPR per patient after three ICSI-IVF cycles was 68.6%. The CPR for patients with or without associated adenomyosis was 19 and 82.4%, respectively (P= 0.01). In addition, a patient age over 35 years (P= 0.02) and anti-Mullerian hormone serum level under 2 ng/ml (P= 0.02) were associated with a decreased CPR per patient. At multivariable analysis, adenomyosis [HR = 0.34, 95% CI (0.12-0.99), P= 0.49] was associated with a decreased CPR. CONCLUSIONS: Our data confirm that ICSI-IVF offers a high CPR per patient. However, determinant factors of CPR should be taken into account when informing couples of their options.

[Infertility treatments after gynecologic cancers and indications of ovarian tissue cryopreservation]. / Traitements de l'infertilité après traitement d'un cancer gynécologique et indication de la congélation du tissu ovarien.

Increasing numbers of young people are surviving cancer, but treatment can affect their reproductive function. Female fertility is more difficult to preserve than male fertility. Fertility-sparing treatments may be possible for some women. For others, embryo cryopreservation is the only established option, provided cancer therapy can be postponed. However, cryopreservation of eggs or ovarian tissue is now becoming a real possibility. Medically assisted reproductive options for cancers survivors include ovarian stimulation, IVF and oocyte donation. Gestational surrogacy and adoption are other possibilities.

[Medical treatment for recurrent miscarriages]. / Les traitements médicaux des avortements spontanés à répétition.

Effective proven therapies for recurrent abortions are few. Aspirin, prednisone and heparin are most commonly utilized but are not clearly proven to outperform expectant management except in case of antiphospholipid syndrome. Progesterone supplementation is unproven in effectiveness but of low risk. Therapeutic intervention should be strongly guided by the principle of doing no harm to the patient.