Impact of endometriosis on oocyte morphology in IVF-ICSI: retrospective study of a cohort of more than 6000 mature oocytes.

BACKGROUND: Infertility associated with endometriosis can be explained by several non-exclusive mechanisms. The oocyte plays a crucial role in determining embryonic competence and this is particularly relevant for in vitro fertilization (IVF) outcomes. According to some authors, the morphology of oocytes could also be a non-invasive marker of oocyte quality. The aim of this study was to evaluate the relationship between endometriosis and oocyte morphology after controlled ovarian stimulation for intracytoplasmic sperm injection (ICSI) on a large oocyte cohort. METHODS: Single-center comparative retrospective study in the academic In Vitro Fertilization (IVF) unit of the Lille University Hospital. A total of 596 women treated for IVF-ICSI with ejaculated spermatozoa for sperm alterations were included. They were classified as endometriosis (n = 175) or control groups (n = 401). The morphological evaluation of 2,016 mature oocytes from 348 cycles of patients with endometriosis was compared with that of 4,073 mature oocytes from 576 control cycles. The main outcome measures were Average Oocyte Quality Index (AOQI) and metaphase II oocyte morphological scoring system (MOMS). Comparison of groups was carried out by a mixed linear model and by a generalized estimation equation model with a "patient" random effect to consider that a patient might have several attempts. RESULTS: No difference in AOQI and MOMS scores was found between endometriosis and control women (adjusted p = 0.084 and 0.053, respectively). In case of endometriosis, there were significantly fewer metaphase II oocytes retrieved, embryos obtained, grade 1 embryos and number of cumulative clinical pregnancies compared to controls. In the endometriosis group, endometriosis surgery was associated with a reduced number of mature oocytes retrieved, and the presence of endometrioma(s) was associated with some abnormal oocyte shapes. Nevertheless, no difference concerning the AOQI and MOMS scores was found in these subgroups. CONCLUSION: Endometriosis does not have a negative impact on oocytes' morphology in IVF-ICSI. TRIAL REGISTRATION: On December 16, 2019, the Institutional Review Board of the Lille University Hospital gave unrestricted approval for the anonymous use of all patients' clinical, hormonal and ultrasound records (reference DEC20150715-0002).

[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 to Choose the Optimal Starting Dose of Clomiphene Citrate (50 or 100 mg per Day) for a First Cycle of Ovulation Induction in Anovulatory PCOS Women?

RESEARCH QUESTION: Clomiphene citrate (CC) is one of the first-line treatments for ovulation induction in women with anovulatory polycystic ovary syndrome (PCOS). However, nearly 1 out of 2 women is resistant to 50 mg/day of CC. The objective of this study is to investigate the clinical, biological, and/or ultrasound factors that may predict the resistance to 50 mg/day of CC in the first cycle of treatment in women with anovulatory PCOS. This would make it possible to identify PCOS patients to whom the dose of 100 mg/day would be offered as of the first cycle. DESIGN: A retrospective and monocentric study was conducted on 283 women with anovulatory PCOS who required the use of ovulation induction with CC (903 cycles). RESULTS: During the first cycle of treatment, 104 patients (36.8%) were resistant to 50 mg/day of CC. Univariate regression analysis showed that patients who resisted 50 mg/day of CC had significantly higher BMI, waist circumference, serum levels of AMH, total testosterone, Δ4-androstenedione, 17-OHP, and insulin (p < 0.05), compared to patients ovulating with this dose. Serum levels of SHBG were significantly lower in patients resistant to 50 mg/day (p < 0.05). After multivariate analysis, only AMH and SHBG remained statistically significant (p = 0.01 and p = 0.001, respectively). However, areas under the ROC curves were weak (0.59 and 0.68, respectively). CONCLUSION: AMH and SHBG are the only two parameters significantly associated with the risk of resistance to 50 mg/day of CC. However, no satisfactory thresholds have been established to predict resistance to 50 mg CC.

Systematic use of long-acting intramuscular progesterone in addition to oral dydrogesterone as luteal phase support for single fresh blastocyst transfer: A pilot study.

Objective: The need of luteal support after FET is no longer to be proven. Different routes of progesterone administration are available with interindividual differences in metabolization and serum progesterone levels, the latter being highly correlated with pregnancy and delivery rates. The administration of 2 different routes of progestogen significantly improves success rates in FET. The aim of the current study was to investigate the added value to combine intramuscular administration of progesterone to dydrogesterone in fresh embryo transfer. Methods: This is a retrospective study from prospectively collected data. Patient, aged between 18 and 43 years old, had received a fresh blastocyst transfer between January 2021 and June 2021. In the first group, all patients received only oral dydrogesterone 10mg, three times a day, beginning the evening of oocyte retrieval. In the second group, patients received, in addition to dydrogesterone, a weekly intramuscular injection of progesterone started the day of embryo transfer. Primary endpoint was ongoing pregnancy rate. Results: 171 fresh single blastocyst transfers have been performed during this period. 82 patients were included in "dydrogesterone only" and 89 patients in "dydrogesterone + IM". Our two groups were comparable except for body mass index. After adjustment on BMI, our two groups were comparable regarding implantation rate, early pregnancy rate (46.1 versus 54.9, OR 1.44 [0.78; 2.67], p=0.25) miscarriage rate, ongoing pregnancy rate (30.3 versus 43.9, OR 1.85 [0.97; 3.53] p= 0.06). Conclusion: Using systematically long acting intramuscular progesterone injection in addition to oral dydrogesterone as luteal phase support seems to have no significant impact on IVF outcomes when a single fresh blastocyst transfer is performed.

Could Cytochrome P450 2D6, 3A4 and 3A5 Polymorphisms Explain the Variability in Clinical Response to Clomiphene Citrate of Anovulatory PCOS Women?

Introduction: Cytochrome P450 2D6, 3A4 and 3A5 are involved in the metabolism of many drugs. These enzymes have a genetic polymorphism responsible for different metabolic phenotypes. They play a role in the metabolism of clomiphene citrate (CC), which is used to induce ovulation. Response to CC treatment is variable, and no predictive factors have thus far been identified. Objective: To study a possible link between the cytochrome P450 2D6, 3A4 and 3A5 polymorphisms and clinical response to CC. Study Design: Seventy-seven women with anovulatory Polycystic Ovarian Syndrome (PCOS) treated with CC were included which determined their cytochrome P450 2D6, 3A4 and 3A5 genotypes and used the results to predict ovarian response to this drug. Predicted responses based on the cytochrome genotypes were compared with the observed clinical responses using the calculation of a weighted Kappa coefficient. Main Outcome Measures: Number of dominant follicles assessed by ultrasound at the end of the follicular phase and confirmation of ovulation by blood progesterone assay in the luteal phase. Results: Concordance between the predicted and observed responses for the combination of the three cytochromes was 36.71%, with a negative Kappa coefficient (K = -0.0240), which corresponds to a major disagreement. Similarly, for predictions based on the cytochrome P450 2D6 genotype alone, only 39.24% of predictions were verified (coefficient K = -0.0609). Conclusion: The genetic polymorphism of cytochromes P450 2D6, 3A4 and 3A5 does not appear to influence clinical response to CC used to induce ovulation in anovulatory PCOS women.