[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.

Secondary infertility with a history of vaginal childbirth: Ready to have another one?

INTRODUCTION: Up to 30% of couples may face secondary infertility. The impact of ectopic pregnancy, spontaneous abortion, pregnancy termination or live birth with caesarean section may impair further fertility in different ways. However, secondary infertility after physiological vaginal life childbirth has been little studied. The aim of this study was to describe the population and the fertility issues and analyze the predictive factors of success in in vitro fertilization in women presenting secondary infertility after a physiological vaginal childbirth. MATERIAL AND METHODS: This single-centre retrospective study included women aged 18-43 years consulting between 2013 and 2020 for secondary infertility in a couple having already had previous vaginal life childbirth. Couples' characteristics, management decision after the first consultation and IVF outcomes were analyzed. RESULTS: Secondary infertility was found in 286 couples, out of whom 138 had a history of vaginal life childbirth. Population was characterized by an advanced female age and overweight. After the first consultation, IVF was performed in only 40% of couples. No predictive factor of live birth was found. CONCLUSION: Our study shows that in couples with secondary infertility after prior physiological delivery cigarette smoking is frequent in male partners, and ovarian reserve markers are altered. However, no statistically significant predictive factor of live birth after IVF treatment has been identified. Further large prospective studies are necessary.

Artificial intelligence in medicine: A matter of joy or concern?

Artificial Intelligence (AI), a concept which dates back to the 1950s, is increasingly being developed by many medical specialties, especially those based on imaging or surgery. While the cognitive component of AI is far superior to that of human intelligence, it lacks consciousness, feelings, intuition and adaptation to unexpected situations. Furthermore, fundamental questions arise with regard to data security, the impact on healthcare professions, and the distribution of roles between physicians and AI especially concerning consent to medical care and liability in the event of a therapeutic accident.

Outcomes of fertility preservation in women with endometriosis: comparison of progestin-primed ovarian stimulation versus antagonist protocols.

BACKGROUND: PPOS protocols, initially described for FP in women with cancer, have many advantages compared to antagonist protocols. PPOS protocols were not evaluated for women with endometriosis. The objective of the study was to describe fertility preservation outcomes in women with endometriosis and to compare an antagonist protocol with a Progestin-Primed Ovarian Stimulation (PPOS) protocol. METHOD: We conducted a prospective cohort study associated with a cost-effectiveness analysis in a tertiary-care university hospital. The measured outcomes included the numbers of retrieved and vitrified oocytes, and direct medical costs. In the whole population, unique and multiple linear regressions analysis were performed to search for a correlation between individual characteristics and the number of retrieved oocyte. RESULTS: We included 108 women with endometriosis who had a single stimulation cycle performed with either an antagonist or a PPOS protocol. Overall, 8.1 ± 6.6 oocytes were retrieved and 6.4 ± 5.6 oocytes vitrified per patient. In the multiple regression model, age (p = 0.001), prior ovarian surgery (p = 0.035), and anti-Mullerian hormone level (p = 0.001) were associated with the number of retrieved oocytes. Fifty-four women were stimulated with an antagonist protocol, and 54 with a PPOS protocol. A mean of 7.9 ± 7.4 oocytes were retrieved in the antagonist group and 8.2 ± 5.6 in the PPOS group (p = 0.78). A mean of 6.4 ± 6.4 oocytes were vitrified in the antagonist group and 6.4 ± 4.7 in the PPOS group (p = 1). In the cost-effectiveness analysis, the PPOS protocol was strongly dominant over the antagonist protocol. CONCLUSION: Fertility preservation procedures are feasible and effective for patients affected by endometriosis. Antagonist and PPOS protocols were associated with similar results but the medico-economic analysis was in favor of PPOS protocols.

Proportion of Cytotoxic Peripheral Blood Natural Killer Cells and T-Cell Large Granular Lymphocytes in Recurrent Miscarriage and Repeated Implantation Failure: Case-Control Study and Meta-analysis.

We aimed to compare the proportion of peripheral blood natural killer (NK) cells (CD3-CD56+) and T-cell large granular lymphocytes (CD8+CD57+) during preconception in a homogenous group of women with unexplained well-defined recurrent miscarriage (RM) and repeated implantation failure (RIF) vs healthy controls in relation to pregnancy outcomes. This case-control study followed by a literature review and meta-analysis was conducted in three university hospitals. Patients and controls were consecutively recruited from December 2015 to October 2017. In total, 115 women were included in the study: 54 with RM, 41 with RIF and 20 healthy controls with ≥ 2 term births. Percentages of CD3-CD56+ and CD8+CD57+ cells and sub-populations of CD3-CD56+ cells did not differ between cases and controls. The results for women with subsequent miscarriage did not differ from those with live births. The meta-analysis of the literature showed higher NK-cell proportions in RM [mean difference 3.47 (95% CI 2.94-4.00); p < 0.001] and RIF [mean difference 1.64 (95% CI 0.82-2.45); p < 0.001] than controls. However, the heterogeneity between the different studies was high. The proportion of peripheral blood CD3-CD56+ and CD8+CD57+ cells in the preconception period does not reflect the risk of implantation failure or miscarriage and should not be recommended indicators for the management of RM and RIF. Further prospective large studies are needed to develop a reliable peripheral blood marker of immune deregulation.

[Fertility and deep infiltrating endometriosis]. / Endométriose profonde et fertilité.

Deep infiltrating endometriosis is the most severe form of the disease, defined by infiltration beneath the peritoneum greater than 5mm. It affects several anatomical locations including the bladder, the vesico-uterine cul-de-sac, the torus uterinum, the uterosacral ligament, rectovaginal septum and the colon-rectum. Deep infiltrating endometriosis is associated with infertility. Surgery performed for deep infiltrating endometriosis in the context of pain offers good pregnancy rates either spontaneously or after assisted reproductive technologies. The results are less favorable when digestive tract is involved. IVF performed in the context of deep infiltrating endometriosis allows very satisfactory results and does not entail risks of aggravation of the pathology. There is currently no clear evidence to support either IVF or surgery to manage infertility associated with deep infiltrating endometriosis, but patients should be informed, although a risk of severe complication exists, that surgery is the only way to increase the chances of spontaneous fertility.

[IVF and endometriosis, oocyte donation and fertility preservation]. / Fécondation in vitro et endométriose, don d'ovocytes et cryopréservation ovocytaire.

Endometriosis is a common condition, causing pain and infertility. In infertile woman with superficial peritoneal endometriosis and patent tubes, laparoscopy is recommended, followed by ovarian stimulation alone or in combination with intrauterine inseminations. In case of ovarian or deep endometriosis, the indications of surgery and assisted reproductive technologies remain to be defined precisely. In vitro fertilization is generally proposed after the failure of up to three inseminations, directly for ovarian or deep endometriosis, or in case of an associated factor of infertility, mainly male. Before ovarian stimulation in view to in vitro fertilization, a pretreatment by GnRH agonist for 2 to 6 months or combined contraceptive for 6 to 8 weeks would improve the pregnancy rate. Egg donation is effective in patients with advanced ovarian failure or lack of ovarian response to stimulation. Fertility preservation, especially by oocytes vitrified, must be proposed preventively to women with endometriosis at risk of ovarian failure, without close wish to be pregnant.

Deep infiltrating endometriosis is a determinant factor of cumulative pregnancy rate after intracytoplasmic sperm injection/in vitro fertilization cycles in patients with endometriomas.

OBJECTIVE: To evaluate the cumulative pregnancy rate (CPR) per patient after in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) cycles in patients with endometriomas and to evaluate the determinant factors of CPR per patient. DESIGN: Retrospective study from January 2007 to October 2008. SETTING: Tertiary care university hospital. PATIENT(S): 103 patients who had undergone IVF treatment, comprising isolated endometriomas (n = 30) and endometriomas with associated deep infiltrating endometriosis (DIE) (n = 73). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate after IVF-ICSI cycle. RESULT(S): The total number of cycles was 162, and the median number of cycles per patient was 1 (1 to 5). Fifty-eight women (56.3%) became pregnant. The total number of endometriomas and size of the largest endometrioma and bilateral endometriomas had no impact on the CPR per patient. Using multivariable analysis, the associated DIE and antimüllerian hormone serum level (≤ 1 ng/mL) were independent factors associated with a decrease in the pregnancy rate per patient. Overall, the CPR per patient was 73.7%, and it increased until the third cycle with no benefit for additional cycles. The CPR per patient for women with isolated endometriomas and women with endometriomas and associated DIE was 82.5% and 69.4%, respectively. CONCLUSION(S): Associated DIE has a negative impact on assisted reproduction results in patients with endometriomas. Moreover, our data show that after three IVF-ICSI cycles the CPR per patient is not improved and that surgery should be considered.

Results of first in vitro fertilization cycle in women with colorectal endometriosis compared with those with tubal or male factor infertility.

This retrospective study of women undergoing IVF (29 with colorectal endometriosis, 157 with tubal factor infertility, and 340 with male factor infertility) found similar fertility outcomes between the groups.

Determinants of pregnancy rate in the donor oocyte model: a multivariate analysis of 450 frozen-thawed embryo transfers.

BACKGROUND: Conflicting results have been published about the determinants of pregnancy after oocyte donation (OD). We used the OD model to determine predictive factors of pregnancy in the recipient after frozen-thawed embryo transfer (FTET) in a specific series where all the embryos were cryopreserved without any prior selection for fresh transfer. METHODS: We report a retrospective study in a university tertiary care center. Multivariate analysis and logistic regression were used to identify predictive factors of pregnancy in a series of 450 OD FTET cycles in 198 infertile women between January 1992 and December 2006. RESULTS: The mean (+/-SD) recipient age was 35.7 (+/-4.5). Impaired ovarian function was the main indication for OD. The mean +/- SD (range) number of embryos transferred was 1.65 +/- 0.5 (1-3). Overall clinical pregnancy, implantation and delivery rates were 30, 18 and 23%, respectively. After univariate analysis, pregnancy rates were significantly higher in recipients under 35 years, in women with a body mass index (BMI) <30 kg/m(2), in women with an endometrial thickness of > or =8 mm, in amenorrheic women and in women not receiving pituitary down-regulation before endometrial preparation. Using multivariate analysis, the BMI, endometrial thickness and the use of pituitary down-regulation were independent predictors of pregnancy, regardless of age. CONCLUSIONS: This study supports that endometrial thickness of <8 mm, obesity and the use of GnRH analogue pituitary down-regulation before endometrial priming negatively impact pregnancy rates, independently of the recipient's age.

Functional results and quality-of-life after bilateral sacrospinous ligament fixation for genital prolapse.

OBJECTIVES: To evaluate intra- and post-operative complications, anatomical results, quality-of-life and sexuality after bilateral sacrospinous ligament fixation (SSLF). STUDY DESIGN: Retrospective longitudinal study. Between March 2001 and September 2003, 51 women with stage III or IV genital prolapse underwent bilateral SSLF at the gynecology and obstetrics university department of Tenon Hospital, Paris, France. The population characteristics were as follows: mean age (+/-S.D.) was 64+/-10 years. Mean+/-SD BMI was 25+/-4 and median (range) parity was (0-12). Forty-eight (94%) women were post-menopausal, and one-third had previously undergone hysterectomy. Intra- and post-operative complications and anatomical results were recorded. Quality-of-life questionnaires (IIQ-7 and PISQ-12) and numerical analog scales were administered as well as nine questions on digestive symptoms. RESULTS: The overall complication rate was 17.3%, with rectal injury in one (1.9%) women. One pararectal hematoma necessitated repeat surgery. Anterior vaginal wall prolapse (Ba=-1) occurred in three women, at 10, 16 and 19 months, but did not necessitate further surgery. The global patient satisfaction rate after bilateral SSLF was 93% (47 women). Digestive symptoms were improved after bilateral SSLF. The mean pre- and post-operative scores on the IIQ-7 and PISQ-12 questionnaires were 41+/-27 and 10+/-18 (p<0.0001), and 62+/-14 and 72+/-11 (p<0.0001), respectively. Posterior perineorrhaphy was associated with significantly altered sexuality. CONCLUSION: These results support the feasibility of bilateral SSLF: intra- and post-operative complication rates are acceptable, quality-of-life and sexuality are improved, and bowel function is unaffected.

Luteinizing hormone concentrations after gonadotropin-releasing hormone antagonist administration do not influence pregnancy rates in in vitro fertilization-embryo transfer.

OBJECTIVE: To determine the impact of circulating LH concentrations during controlled ovarian hyperstimulation on the outcome of IVF. DESIGN: Retrospective study. SETTING: University hospital. PATIENT(S): Two-hundred seventy women who had a short stimulation protocol with GnRH antagonist and ovarian stimulation with recombinant FSH (rFSH). INTERVENTION(S): GnRH antagonist and rFSH were administered SC; blood samples were collected on the day of GnRH antagonist administration, 1 day after, and on the day of hCG administration. MAIN OUTCOME MEASURE(S): A threshold of 0.5 IU/L on the day of hCG was chosen to discriminate between women with LH concentrations 0.5 IU/L (group B, n = 151). RESULT(S): The two groups were comparable with regard to the clinical parameters. In group A, significantly lower LH concentrations were observed on day 9 of the cycle and on the day of hCG administration. The numbers of oocytes retrieved, embryos obtained, and embryos cryopreserved were significantly higher in group A compared with group B. The proportion of clinical pregnancies was similar in the two groups (21.1% vs. 22.7 % per ET). CONCLUSION(S): In GnRH antagonist and rFSH protocols, suppressed serum LH concentrations do not have any influence on the final stages of follicular maturation, pregnancy rates, or outcomes.

[Cushing's syndrome during pregnancy]. / Le syndrome de Cushing durant la grossesse.

The rare association of Cushing's syndrome and pregnancy is explained by the amenorrhea and sterility inherent to the syndrome. In the literature, 125 cases have been reported: 30 cases of early diagnosis and 95 others diagnosed in the second half of pregnancy. AT THE START OF PREGNANCY: When hypercorticism exists before pregnancy it is hardly secretory. Its diagnosis, at an early stage, is not hindered by the hormone modifications of pregnancy. Its aetiological treatment raises the problem of the compatibility in pursuing the latter. IN THE SECOND HALF OF PREGNANCY: The positive and aetiological diagnoses of Cushing's syndrome are difficult and its prevalence may therefore be underestimated. The evocative clinical signs are unspecific: excessive weight gain, hypertension of pregnancy and gestational diabetes. The 24-hour free hypercortisoluria and the absence of dexamethasone inhibition are of little diagnostic value after the 14th week of amenorrhea. The positive diagnosis therefore relies essentially on the abolition of the circadian rhythm of cortisol. The biological hyperandrogenia commonly observed is not discriminating. Adrenal aetiologies are frequent. Imaging must be performed to eliminate an adrenocortical tumor. PROGNOSIS: The maternal prognosis depends on the hypertension, preeclampsia, diabetes and the complications of Cushing's syndrome. It depends on the activity of the hypercorticism and its early aetiological treatment, which must not be delayed after pregnancy. The foetal prognosis depends on the maternal prognosis. It is represented by preterm delivery, hypotrophy and death of the foetus in utero. The therapeutic management must be symptomatic and aetiologic, maternal and obstetrical.

[Cancer and Pregnancy: the point of view of the obstetrician]. / Cancer et grossese: le point de vue de l'obstétricien.

Onset of malignancy during pregnancy is distressing for the future parents and raises thorny problems for the oncologist and obstetric gynecologist. Many diagnostic and therapeutic approaches cannot be used. Some first-line reference treatments are known to cause fetal loss or severe birth defects, yet any delay in treatment may unacceptably worsen the maternal prognosis. In the absence of large randomized trials and cohort studies, it is difficult to know how best to manage these patients. An estimated one in ten thousand pregnancies are associated with malignancies, especially gynecologic tumors (cervix, breast, ovary), lymphomas, melanomas, brain tumors and leukemia. The obstetrician, in close collaboration with the oncologist, has a major role in choosing the most appropriate diagnostic and therapeutic strategy, and must keep the couple fully informed. Importantly, improvements in cancer cure rates and the development of conservative treatments mean that many of these young women can hope to start a new pregnancy after their treatment. The optimal interval between cure and conception must be carefully weighed up by a multidisciplinary team including oncologists and obstetric gynecologists. Chemotherapy, pelvic radiation therapy, and gynecologic surgery can impact not only on fertility but also on the course of a next pregnancy (increased risk of miscarriage and premature delivery, etc.). The obstetrician must take these risks into account.

Operable Stages IB and II cervical carcinomas: a retrospective study comparing preoperative uterovaginal brachytherapy and postoperative radiotherapy.

PURPOSE: To evaluate our data concerning prognostic factors and treatment toxicity in a series of operable cervical carcinomas. METHODS AND MATERIALS: Between May 1972 and January 1994, 414 patients with cervical carcinoma, staged according to the 1995 FIGO staging system (286 Stage IB1, 38 Stage IB2, 56 Stage IIA, and 34 Stage IIB with 1/3 proximal parametrial involvement), underwent radical hysterectomy with (n = 380) or without (n = 34) bilateral pelvic lymph node dissection (N+: n = 68). Group I included 168 patients who received postoperative radiation therapy (RT): 64 patients had low-dose-rate vaginal brachytherapy with a median total dose (MTD) of 50 Gy; 93 patients had external beam pelvic RT (EBPRT) with an MTD of 45 Gy over 5 weeks, followed by low-dose-rate vaginal brachytherapy (MTD: 20 Gy); and 11 patients had EBPRT alone (MTD: 50 Gy over 6 weeks). Group II included 246 patients treated with preoperative low-dose-rate uterovaginal brachytherapy (MTD: 65 Gy); 32 of these 246 patients also received postoperative EBPRT (MTD: 45 Gy over 5 weeks) delivered to the parametria and pelvic nodes. Mean follow-up from the beginning of treatment was 106 months. RESULTS: First events included isolated locoregional recurrences (35 patients), isolated distant metastases (27 patients), and locoregional recurrences with synchronous metastases (13 patients). The 10-year disease-free survival (DFS) rate was 88% for Stage IB1, 44% for Stage IB2, 65% for Stage IIA, and 48% for Stage IIB. Multivariate analysis showed that independent factors influencing the probability of DFS were as follows: cervical site (exocervical or endocervical vs. both endo- and exocervical, relative risk [RR]: 1.77, p = 0.047), vascular space invasion (no vs. yes, RR: 1.95, p = 0.041), age (>51 years vs. 1 cm: 83% vs. 41%, respectively, p = 0.001). The overall postoperative complication rate was 10% in Group I and 9% in Group II (p = 0.7). The rate of postoperative ureteral complications requiring surgical intervention was lower in Group I than in Group II (0.6% vs. 2.3%, respectively, p = 0.03). The overall 10-year rate for Grade 3 and 4 late radiation complications was 10.4%. Postoperative EBPRT significantly increased the 10-year rate for Grade 3 and 4 late radiation complications (yes vs. no: 22% vs. 7%, respectively, p = 0.0002). CONCLUSION: The prognosis for patients with cervical carcinoma was not influenced by the sequence of adjuvant RT (preoperative uterovaginal brachytherapy vs. postoperative RT) for Stages IB, IIA, and IIB with 1/3 proximal parametrial involvement. However, postoperative EBPRT increased the risk of late radiation complications.