Does surgery for colorectal endometriosis prior to IVF±ICSI have an impact on cumulative live birth rates?

RESEARCH QUESTION: Does colorectal endometriosis surgery prior to IVF ± intracytoplasmic sperm injection (ICSI) impact cumulative live birth rates? DESIGN: This retrospective, monocentric study (Lille University Hospital) was conducted between 1 January 2007 and 31 December 2018. Two groups of patients from the JFIV database were included: a group undergoing IVF±ICSI alone (120 patients, 215 oocyte retrievals), and a group undergoing surgery and then IVF±ICSI (69 patients, 109 oocyte retrievals). The mode of management was decided after a multidisciplinary team meeting. Different criteria such as age (cut-off 35 years), anti-Müllerian hormone concentration (cut off 2 ng/ml), imaging results and the patient's symptomatology were considered: the most symptomatic patients underwent surgery prior to IVF±ICSI. The cumulative clinical pregnancy and live birth rates obtained after four IVF attempts were estimated and compared between the two groups using competing risk survival methods. RESULTS: The cumulative live birth rates after four IVF attempts in the two groups were not statistically significantly different (50.8% in the IVF±ICSI group versus 52.2% in the surgery followed by IVF±ICSI group, P = 0.43). The results for the cumulative clinical pregnancy rates were the same (56.7% in the IVF±ICSI group versus 58% in the surgery followed by IVF±ICSI group, P = 0.47). CONCLUSION: The study shows that cumulative live birth and pregnancy rates were similar in infertile patients with colorectal endometriosis who underwent IVF±ICSI either with or without prior colorectal endometriosis surgery.

Pain assessment in women with or without endometriosis during the IVF process: a prospective study.

RESEARCH QUESTION: How does the typology and effect of pain vary between infertile patients with or without endometriosis during the different stages of the IVF process? DESIGN: A prospective, monocentric, observational cohort study was conducted at Lille University Hospital between November 2019 and June 2021. The study was proposed to all patients starting an IVF cycle. Pain assessment questionnaires using validated scales (about type of pain, without specific location), were completed by patients at key points during IVF: before starting treatment, at the end of stimulation and on the day of oocyte retrieval. RESULTS: A total of 278 patients were analysed: 73 patients with endometriosis and 205 without. At the start of the IVF process, patients with endometriosis had higher pain scores than disease-free women (mean numerical scale score 3.47 versus 1.12 [P < 0.0001]) and 17.81% of patients with endometriosis had neuropathic pain. For mental disorders before starting treatment, 22% of patients with endometriosis had suspected or confirmed depression, and 33% had anxiety compared with 8% and 20% in patients without endometriosis, respectively. During IVF, for patients without endometriosis, pain increased significantly between the baseline, the end of stimulation and on the day of retrieval (P ≤ 0.05). In patients with endometriosis, however, pain did not significantly vary during these times. CONCLUSION: Endometriosis is associated with higher pain scores, but no increase in pain was observed during IVF for these patients. It seems essential to screen and characterize pain phenotypes in all patients before starting treatment and during stimulation to improve pain management.

Comparison of two endometrial preparation methods for frozen-thawed embryo transfer in anovulatory PCOS patients: Impact on miscarriage rate.

OBJECTIVE: Some studies have suggested that patients with polycystic ovary syndrome (PCOS) are at high risk of miscarriage. However, this still remains controversial. Several potential factors might explain this association: obesity, hyperinsulinemia and hyperandrogenism. Artificial and stimulated cycles appear to be comparable for endometrial preparation in frozen-thawed embryo transfer (FET) in PCOS patients. Only a few studies have assessed miscarriage rates specifically in PCOS. We have evaluated the impact of endometrial preparation on FET outcomes in anovulatory PCOS patients. METHODS: A retrospective cohort study was conducted at the Lille University Hospital, including 255 FET cycles in 134 PCOS patients between January 2011 and December 2017. PCOS was defined by the presence of at least two of the three Rotterdam's criteria. Patients were under 35 years old. Two endometrial preparation protocol were studied: stimulated cycle (gonadotropins on the second day of the cycle and luteal phase support including natural progesterone 600 mg/day) and artificial cycle (6 mg oral estradiol valerate and 800 mg micronized vaginal progesterone daily). RESULTS: 137 FET were performed under stimulated cycle and 118 FET under artificial cycle. Early pregnancy rates (30% versus 37.3%, p = NS), miscarriage rates (22% versus 25%, p = NS) and live birth rates (23.4% versus 26.3%, p = NS) were similar. CONCLUSIONS: In anovulatory PCOS women, the type of endometrial preparation does not influence FET outcomes, specifically regarding the miscarriage rate.

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.

Weekly intramuscular progesterone for luteal phase support in women receiving oocyte donation is associated with a decreased miscarriage rate.

RESEARCH QUESTION: To determine whether adding intramuscular to vaginal administration of progesterone reduces miscarriage rates compared with those of vaginal administration alone for luteal phase support in women receiving oocyte donation and to determine the best time to introduce intramuscular progesterone. DESIGN: Retrospective analysis of miscarriage rates in women receiving oocyte donation. Recipients underwent endometrial preparation by hormone replacement treatment. Vaginal progesterone alone or associated with intramuscular progesterone was used for luteal support. RESULTS: This study analysed 186 oocyte donation cycles from January 2016 to May 2018 with embryo transfer on Day 2 or 3 and vaginal progesterone administration: 106 embryo transfer cycles with vaginal progesterone alone, 29 with weekly intramuscular progesterone added once the human chorionic gonadotrophin (HCG) assay was positive, and 51 with weekly intramuscular progesterone added the evening of embryo transfer. The rates of positive HCG assays, biochemical pregnancies and clinical pregnancies did not differ between the treatment groups. The miscarriage rate was significantly lower when intramuscular progesterone began the evening of embryo transfer than with vaginal administration alone (16.7% versus 47.0%, respectively; P = 0.049 after Bonferroni correction). The live birth rate was higher when intramuscular progesterone began the evening of embryo transfer than with vaginal administration alone (37.3% versus 16.0%, respectively; P = 0.009 after Bonferroni correction). CONCLUSIONS: Adding intramuscular to vaginal progesterone administration appears to decrease the miscarriage rate and increase the live birth rate in oocyte donations. The initiation of intramuscular progesterone is most beneficial when it is introduced the evening of embryo transfer.

Comparison between pulsatile GnRH therapy and gonadotropins for ovulation induction in women with both functional hypothalamic amenorrhea and polycystic ovarian morphology.

CONTEXT: Ovulation induction in patients having both functional hypothalamic amenorrhea (FHA) and polycystic ovarian morphology (PCOM) has been less studied in the literature. As results remain contradictory, no recommendations have yet been established. OBJECTIVE: To compare pulsatile GnRH therapy versus gonadotropins for ovulation induction in "FHA-PCOM" patients and to determine if one treatment strikes as superior to the other. METHODS: A 12-year retrospective study, comparing 55 "FHA-PCOM" patients, treated either with GnRH therapy (38 patients, 93 cycles) or with gonadotropins (17 patients, 53 cycles). RESULTS: Both groups were similar, defined by low serum LH and E2 levels, low BMI, excessive follicle number per ovary and/or high serum AMH level. Ovulation rates were significantly lower with gonadotropins (56.6% versus 78.6%, p = 0.005), with more cancellation and ovarian hyper-responses (14% versus 34% per initiated cycle, p < 0.005). Pregnancy rates were significantly higher with GnRH therapy, whether per initiated cycle (26.9% versus 7.6%, p = 0.005) or per patient (65.8% versus 23.5%, p = 0.007). CONCLUSION: In our study, GnRH therapy was more successful and safer than gonadotropins, for ovulation induction in "FHA-PCOM" patients. If results were confirmed by prospective studies, it could become a first-line treatment for this population, just as it is for FHA women without PCOM.

Does polycystic ovarian morphology influence the response to treatment with pulsatile GnRH in functional hypothalamic amenorrhea?

BACKGROUND: Pulsatile GnRH therapy is the gold standard treatment for ovulation induction in women having functional hypothalamic amenorrhea (FHA). The use of pulsatile GnRH therapy in FHA patients with polycystic ovarian morphology (PCOM), called "FHA-PCOM", has been little studied in the literature and results remain contradictory. The aim of this study was to compare the outcomes of pulsatile GnRH therapy for ovulation induction between FHA and "FHA-PCOM" patients in order to search for an eventual impact of PCOM. METHODS: Retrospective study from August 2002 to June 2015, including 27 patients with FHA and 40 "FHA-PCOM" patients (85 and 104 initiated cycles, respectively) treated by pulsatile GnRH therapy for induction ovulation. RESULTS: The two groups were similar except for markers of PCOM (follicle number per ovary, serum Anti-Müllerian Hormone level and ovarian area), which were significantly higher in patients with "FHA-PCOM". There was no significant difference between the groups concerning the ovarian response: with equivalent doses of GnRH, both groups had similar ovulation (80.8 vs 77.7 %, NS) and excessive response rates (12.5 vs 10.6 %, NS). There was no significant difference in on-going pregnancy rates (26.9 vs 20 % per initiated cycle, NS), as well as in miscarriage, multiple pregnancy or biochemical pregnancy rates. CONCLUSION: Pulsatile GnRH seems to be a successful and safe method for ovulation induction in "FHA-PCOM" patients. If results were confirmed by prospective studies, GnRH therapy could therefore become a first-line treatment for this specific population, just as it is for women with FHA without PCOM.

Is the suppressive effect of cyproterone acetate on serum anti-Müllerian-hormone levels in women with polycystic ovary syndrome stronger than under oral contraceptive pill?

OBJECTIVE: To compare the suppressive effect of anti-androgen therapy by cyproterone acetate (CPA) and by oral contraceptive pill (OCP) on anti-müllerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS) in order to detect a putative direct anti-androgen effect on AMH excess. METHODS: This is a prospective longitudinal study including 58 women with PCOS between January 2010 and April 2014 at the Lille University Hospital. A total of 47 women with clinical hyperandrogenism were treated by CPA (50 mg/d was administered 20 days out of 28) and 11 women with PCOS but without clinical hyperandrogenism received OCP. RESULT(S): Serum AHM levels at baseline were similar in CPA and OCP groups (median [5-95th percentiles]: 60.4 pmol/l [25.1-200.2] versus 58 pmol/l [27.6-100], respectively, p = 0.39). After 3 months of treatment, serum AMH levels decreased significantly by 28% ± 20% and by 22% ± 27% in CPA and OCP groups, respectively. The decrease under both treatments was similar (p = 0.48). CONCLUSION(S): That any anti-androgen effect could be observed on AMH in our CPA group in addition to the gonadotropin-suppressing effect suggests that either androgens are not involved in AMH regulation or that they act by interfering with gonadotropin effects on granulosa cells.