[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.

How is functionning the Ethical Review Board « Comité d'Ethique Pour La Recherche En Obstétrique Et Gynécologie ¼ (CEROG) ?

INTRODUCTION: The French College of Gynecology and Obstetrics (CNGOF) has created an Ethical Review Board called the CEROG that aim to ensure the research projects are in conformity with the regulation and the laws, as well as to allow their publication in international scientific journals. The aim of this work was to analyze the work of this committee through the application received and to review the ethical procedures required by type of research project. METHODS: We conducted a national retrospective study of all applications from 2018 to 2021 received by the CEROG Ethical Review Board. Each application must contain a verification of conformity with the MR004 regulation, a submission form and an information form to the patients involved. At reception, the documents are anonymized and then addressed to the members of one of the two independent sections (Obstetric and Prenatal diagnosis or Gynecology and Assisted Reproductive Therapy). RESULTS: Two hundred and sixty applications were received, including 52% in the Gynecology section and 48% in the Obstetrics' section. Only 10% (14/136) and 8% (10/124) were disapproved, respectively. In total, 35% of the applications to the Gynecology section leaded to publications in scientific journals but only 23% did so in the Obstetrics section. Most publications (60.8%) were in low impact factors journals (rank D and E). CONCLUSION: The Ethical Review Board CEROG is essential to ensure the conformity of the research projects with French regulations and allow fast publication in international journals.

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.

Pregnancy denial and early infant development: a case-control observational prospective study.

BACKGROUND: The denial of pregnancy is the non-recognition of the state of the current pregnancy by a pregnant woman. It lasts for a few months or for the whole pregnancy, with generally few physical transformations. In this study, we will consider the denial of pregnancy as a late declaration of pregnancy (beyond 20 weeks of gestation) as well as a lack of objective perceptions of this pregnancy. The main objective of this study is to explore the relationship between pregnancy denial and the development of the infant (attachment pattern of the infant, early interactions of mother-infant dyads, and early development of the infant). METHODS: The design is a case-control prospective study, which will compare two groups of mother-infant dyads: a "case" group with maternal denials of pregnancy and a "control" group without denials of pregnancy. A total of 140 dyads (mother + infant) will be included in this study (70 cases and 70 controls) and followed for 18 months. The setting is a national recruitment setting with 10 centers distributed all over France. The follow-up of the "cases" and the "controls" will be identical and will occur over 5 visits. It will include measures of the infant attachment pattern, the quality of early mother-infant interaction and infant development. DISCUSSION: This study aims to examine the pathogenesis of pregnancy denial as well as its consequences on early infant development and early mother-infant interaction. TRIAL REGISTRATION: Clinical Trial Number: NCT02867579 on the date of 16 August 2016 (retrospectively registered).

Cell-free fetal DNA versus maternal serum screening for trisomy 21 in pregnant women with and without assisted reproduction technology: a prospective interventional study.

PURPOSE: Cell-free DNA (cfDNA) as a primary screening test has been available for years but few studies have addressed this option in a prospective manner. The question is of interest after reports that maternal serum screening (MSS) is less accurate for pregnancies resulting from assisted reproduction technologies (ART) than for spontaneous pregnancies (SP). METHODS: A prospective interventional study was designed to address the performances of cfDNA compared with MSS in pregnancies with or without ART. Each patient was offered both MSS and cfDNA testing. The primary analysis cohort ultimately included 794 patients with a spontaneous pregnancy (SP) (n = 472) or pregnancy obtained after ART (n = 322). RESULTS: Overall, the false-positive rate and positive predictive value were 6.6% and 8.8% for MSS but 0% and 100% for cfDNA. MSS false-positive rate and positive predictive values were clearly poorer in the ART group (11.7% and 2.6%) than in the SP group (3.2% and 21.1%). The global rates of invasive procedures were 1.9% (15/794) with cfDNA but 8.4% (65/794) if MSS alone was proposed. CONCLUSION: cfDNA achieved better performance than MSS in both spontaneous and ART pregnancies, thus decreasing the number of invasive procedures. Our findings suggest that cfDNA should be considered for primary screening, especially in pregnancies obtained after ART.

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.

[Assisted reproductive technologies and ethics]. / Ethique et assistance médicale à la procréation.

Since the first birth after in vitro fertilization more than 5 million of IVF babies are born in the world. Assisted reproductive technologies captivate the public, they allow maternity without ovary (oocyte donation), without uterus (surrogate mother), paternity without spermatozoids (sperm donation), parentality without limits of age, parentality after death and homoparentality. These technologies arise a lot of ethics questions, the problem is that the answers are not the same all-round the world, laws are based on morals, beliefs, faiths, and convictions. Theses variations arise themselves questions on the value of these non-universal answers.

Pregnancy, somatic complaints and depression: a French population-based study.

OBJECTIVE: Depression during pregnancy is today one of the greatest medical risks for expectant mothers and newborns. It is associated with numerous morbid conditions and with postnatal depression. Identifying depression during pregnancy is therefore a major public health concern, but screening for depression is not routinely carried out in somatic settings. We hypothesized that the presence of numerous somatic complaints contributes to the detection of an increased risk of depression during pregnancy. STUDY DESIGN: A cross-sectional study was conducted on 1000 consecutive pregnant women approached during OB/GYN visits at a general maternity hospital. They were asked to fill out a questionnaire, which contained the Edinburgh Postnatal Depression Scale (EPDS) and a checklist of 18 somatic complaints. RESULTS: The median number of somatic complaints was 5 (interquartile range 3-7). The risk of depression during the 2nd and 3rd trimesters was 18.3% (EPDS score > 10.5). Logistic regression revealed that when the somatic complaints total score moved from 3 to 7, the odds of moving from not-at-risk to at-risk for antenatal depression were multiplied by 2.91. CONCLUSION: Our results call for further research exploring somatic complaints and their link to depression during pregnancy. Until more knowledge is available, we suggest considering that women with a high number of somatic complaints during pregnancy are at high risk for depression and should be referred for further diagnostic clinical assessment and care.

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.

[Treatment options for age-related infertility]. / L'AMP ne compense pas l'effet néfaste de l'age. Techniques d'assistance médicale a la procréation proposées avec l'age (dont le don d'ovocyte).

There has been a consistent trend towards delayed childbearing in most Western countries. Treatment options for age-related infertility includes controlled ovarian hyperstimulation with intrauterine insemination and in vitro fertilization (IVF). A sharp decline in pregnancy rate with advancing female age is noted with assisted reproductive technologies (ART) including IVF. Evaluation and treatment of infertility should not be delayed in women 35 years and older. No treatment other than oocyte donation has been shown to be effective for women over 40 and for those with compromised ovarian reserve, but its pratice is not easy in France hence the procreative tourism. As an increasing number of couples choose to postpone childbearing, they should be informed that maternal age is an important risk factor for failure to conceive.

[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.

Outcome of conventional IVF and ICSI on sibling oocytes in mild male factor infertility.

BACKGROUND: Decisions concerning the treatment choice for assisted reproduction (IVF or ICSI) are usually made after the evaluation of male fertility factors, or after taking into account the results of previous IVF attempts. There are no widely accepted criteria, so decisions for couples with male subfertility are often empirical and may lead to complete fertilization failure after IVF, or to the unnecessary use of ICSI. METHODS: A study was conducted in which half the oocytes from each of 58 couples with moderate oligo +/- astheno +/- teratozoospermia were inseminated (conventional IVF) and the other half microinjected (ICSI). The technique used for subsequent cycles depended on the results of the first cycle. RESULTS: Nineteen of the 58 IVF/ICSI attempts resulted in fertilization after ICSI only (32.8%) and 39 in fertilization after IVF and ICSI (67.2%). For patients with oocyte fertilization only after ICSI, 61.5% of the oocytes microinjected were fertilized. A mean of 2.2 embryos per patient were transferred, leading to eight clinical pregnancies (42.1%). The implantation rate was 21.4%. All subsequent cycles were carried out with ICSI. Couples with oocyte fertilization after both IVF and ICSI had slightly better semen characteristics than those with oocyte fertilization only after ICSI, but this difference was not significant. Overall, no statistically significant difference was observed between IVF and ICSI in sibling oocytes for any of the variables studied: fertilization rate, embryo morphology and rates of development, pregnancy and implantation. Although only small numbers of oocytes or embryos were available for each couple, six couples had lower fertilization rates after IVF and eight had lower embryo quality after IVF. Eight patients had lower sperm quality in the second cycle, and only seven couples underwent subsequent IVF cycles. CONCLUSIONS: This strategy enabled us to avoid 32.8% of complete fertilization failures after IVF, but not to decrease significantly the number of ICSI attempts in subsequent cycles. However, the uncertainties concerning the safety of ICSI suggest that ICSI should be used cautiously and judiciously.