Addition of dydrogesterone to vaginal progesterone and transfer postponement improve outcomes in patients with low progesterone levels in hormonally substituted cycles for frozen-thawed embryo transfer

Purpose: Adding dydrogesterone (DYD) to vaginal micronized progesterone (VMP) and postponing embryo transfer in order to improve outcomes in patients with low progesterone (P) levels in hormonally substituted cycles prior to frozen/thawed embryo transfer (FET). Methods: Endometrial preparation comprised sequential administration of vaginal estradiol until endometrial thickness reached 7 mm, followed by transdermal estradiol combined with 800 mg/day VMP. Our previous analysis of serum P levels on FET day showed that the optimal P level was > 11 ng/mL for live birth. Serum P was measured on day1 (D1) following exogenous VMP introduction in the evening. When P levels were > 11 ng/mL, FET was performed “in phase” on day-2, day-3, or day-5 depending on embryo stage at cryopreservation (n = 139 cycles). When P levels were < 11 ng/mL, DYD 10 mg three times a day orally, was added to VMP and FET was postponed by one day (n = 237 cycles, 63%). The primary endpoint was the comparison of live birth rates (LBR) between the two groups.Results: Mean serum P level on D1 was 10.2 + 3.7 ng/mL. Characteristics of patients in both groups were similar for age, body mass index, endometrial thickness prior to P introduction, quality of transferred embryos, and embryo transfer stage. Regarding the primary endpoint, LBR was similar between the VMP+DYD group and the VMP group (26.1% vs. 27.3%, NS). Conclusion: These results suggest that adding DYD to VMP and postponing the transfer in patients with low P levels in hormonally substituted FET cycles might optimize outcomes

Response to Ovarian Stimulation for Urgent Fertility Preservation before Gonadotoxic Treatment in <i>BRCA</i>-Pathogenic-Variant-Positive Breast Cancer Patients

BRCA 1/2 pathogenic variants increase the risk of developing early and aggressive breast cancers (BC). For these patients, fertility potential can be directly affected by oncologic treatments. In addition, evidence indicates that BRCA-mutated women had a significant reduction in their ovarian reserve. In order to improve their chances of conception after the completion of cancer treatments, fertility preservation should be proposed before the administration of gonadotoxic drugs, ideally by oocyte vitrification after controlled ovarian hyperstimulation (COH). The present investigation aims to assess the ovarian response to COH in BRCA 1/2-pathogenic-variant carriers diagnosed with BC. Patient characteristics and COH outcomes were compared between BRCA-positive (n = 54) and BRCA-negative (n = 254) patients. The number of oocytes recovered did not differ between the two groups. However, the oocyte maturation rate and the number of mature oocytes obtained (7 (4.5–11.5) vs. 9 (5–14) oocytes, p = 0.05) were significantly lower in the BRCA-mutated patients. Although individualized COH protocols should be discussed, BRCA-mutated patients would benefit from FP before BC occurs, in order to cope with the potential accelerated decline of their ovarian reserve, optimize the success rate of FP by repeating COH cycles, and to preserve the feasibility of PGT-M by collecting a large amount of eggs

Response to Ovarian Stimulation for Urgent Fertility Preservation before Gonadotoxic Treatment in BRCA-Pathogenic-Variant-Positive Breast Cancer Patients

BRCA 1/2 pathogenic variants increase the risk of developing early and aggressive breast cancers (BC). For these patients, fertility potential can be directly affected by oncologic treatments. In addition, evidence indicates that BRCA-mutated women had a significant reduction in their ovarian reserve. In order to improve their chances of conception after the completion of cancer treatments, fertility preservation should be proposed before the administration of gonadotoxic drugs, ideally by oocyte vitrification after controlled ovarian hyperstimulation (COH). The present investigation aims to assess the ovarian response to COH in BRCA 1/2-pathogenic-variant carriers diagnosed with BC. Patient characteristics and COH outcomes were compared between BRCA-positive (n = 54) and BRCA-negative (n = 254) patients. The number of oocytes recovered did not differ between the two groups. However, the oocyte maturation rate and the number of mature oocytes obtained (7 (4.5&ndash;11.5) vs. 9 (5&ndash;14) oocytes, p = 0.05) were significantly lower in the BRCA-mutated patients. Although individualized COH protocols should be discussed, BRCA-mutated patients would benefit from FP before BC occurs, in order to cope with the potential accelerated decline of their ovarian reserve, optimize the success rate of FP by repeating COH cycles, and to preserve the feasibility of PGT-M by collecting a large amount of eggs

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