ENDO-REAL: Endometriosis and Reproductive Enhancement with Letrozole

INTERVENTION: Product Name: Letrozole Teva 2,5 mg filmomhulde tabletten, Product Code:PRD12694151, Pharmaceutical Form: FILM‐COATED TABLET, Other descriptive name: , Strength: CONDITION: Therapeutic area: Phenomena and Processes [G] ‐ Reproductive and Urinary Physiological Phenomena [G08] Women with endometriosis undergoing IVF/ICSI PRIMARY OUTCOME: Main Objective: The primary objective of this study is to determine whether letrozole co‐administration during ovarian stimulation for IVF/ICSI can improve the occurrence of a live birth following embryo transfer(s) in patients diagnosed with endometriosis +/‐ adenomyosis. Primary outcome will focus on cumulative live birth per stimulation cycle, including fresh and frozen embryo transfers resulting from the same oocyte aspiration and transferred within 1 year (52 weeks) of randomization. Live birth following fresh embryo transfer and number of ETs needed for successful pregnancy will also be evaluated as an important outcome. Primary end point(s): The primary endpoint is cumulative live birth per stimulation (or IVF/ICSI) cycle, including fresh ET and frozen ETs resulting from the same oocyte aspiration and transferred within 1 year of randomization. Secondary Objective: To compare other reproductive outcomes including implantation, clinical pregnancy, ectopic pregnancy and miscarriage rates between the intervention and control group., To compare pregnancy related complications, neonatal outcomes and congenital abnormalities between the intervention and the control group for women achieving a pregnancy > 24 weeks., To compare total recFSH dose administered and number of stimulation days between the intervention and control group, To compare endometrial thickness and estradiol levels on day of trigger, serum progesterone levels on day of trigger and of ET, number of stimulation days, cumulus oocyte complexes and mature M2 oocytes retrieved, fertilization rates and total number of good quality (EQ 1‐2) blastocysts obtained., To compare pain scores following OPU in both groups., To compare patient QOL between both groups measured at 5 days post OPU and compared to baseline (screening)., To compare evaluate the occurrence of side effects related to letrozole and patient tolerability INCLUSION CRITERIA: Sub/infertile women with a diagnosis of endometriosis (all types/ stages) either by TVUS/ MRI or surgically and an indication for treatment with IVF/ICSI (based on existing guidelines) are eligible for the study., Planned fresh ET following oocyte retrieval, Patient with and without concomitant adenomyosis will be included, The patient must have undergone not more than three consecutive unsuccessful IVF/ICSI cycles since the last ongoing pregnancy (whether fresh and/or several frozen ET resulted from these attempts). Each patient may only participate once., Age = 18 years and < 40 years, Body mass Inde X(BMI) < 35kg/m, Participant should be capable of giving informed consent SECONDARY OUTCOME: Secondary end point(s):Clinical pregnancy rate (at least one gestational sac 4‐6 weeks after transfer) for fresh and frozen ETs. Secondary end point(s):For women achieving a pregnancy > 24 weeks: ? Pregnancy related complications: pre‐eclampsia and pregnancy‐induced hypertension, preterm birth, intrauterine growth restriction, caesarean delivery and obstetric hemorrhage. ? Extreme preterm birth (24‐28 weeks of gestation) ? Still birth and termination of pregnancy ? Gestational age at delivery, Birthweight ? Neonatal admission and mortality ? Major congenital abnormalities Secondary end point(s):Implantation rate (positive serum ßhCG 10‐15 days after transfer) for fresh and frozen ETs. Secondary end point(s):LBR per fresh ET cycle (excluding freeze‐all), defined as live birth at = 24 weeks of gestation. Secondary end point(s):Miscarriage rate (defined as pregnancy loss prior to viability scan and including those confirmed on ultrasound scan up to = 23 weeks 6 days gestation) for fresh and frozen ETs. Secondary end point(s):Number of ETs needed for successful pregnancy Secondary end point(s):Pain score: NRS 1‐10 one to four hours after OPU Secondary end point(s):Patient QOL measured at the day of fresh embryo transfer (OPU +5) and compared to baseline (FertiQOL) Secondary end point(s):Rate of ectopic pregnancy or pregnancy of unknown location for fresh and frozen ETs.