subcutaneous progesterone in frozen- thawed single euploid blastocyst transfer.

Conditions: Infertility

Summary: this is a multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority clinical study in women aged 35 to 42 years. this study will investigate the safety and efficacy of progesterone-ibsa to support euploid embryo blastocyst implantation and early pregnancy after frozen embryo transfer (fet) in a modified natural cycle as a treatment for infertile women. subjects will be randomized to receive either active progesterone-ibsa or crinone 8% for luteal and early pregnancy support and these two groups will be compared.


Eligibility criteria:
inclusion criteria: * subject has given written informed consent; * premenopausal women 35 to 42 years of age at the time of consent (at least 35 \[including day of birthday\] and no more than 42 \[up to the day before their 43rd birthday\]); * valid indication for ivf treatment (i.e. history of infertility according to asrm definition, single women or same-sex couples); * consistent, regular spontaneous ovulatory menstrual cycle with normal length (24-38 days included); * body mass index (bmi) \< 38 kg/m2; * subject with at least one euploid frozen blastocyst from a previous ivf treatment cycle; * less than 3 previous consecutive euploid blastocyst transfers without a life birth; * baseline follicle stimulating hormone (fsh) \ 0.7 ng/ml (within 6 months from screening for subjects requiring a stimulation cycle to obtain a euploid embryo); and estradiol (e2) \< 90 pg/ml and progesterone (p4)\< 1.5 ng/ml at visit 1 (for all subjects); * semen used during ivf(for subjects requiring a stimulation cycle to obtain a euploid embryo) was produced by ejaculation (not surgically derived sperm) from either the partner or from a sperm donor. donor must be 18-40 years of age at the time of collection and compliant with 21 code of regulations (cfr) section 1271 subpart c; * hysterosalpingography, hysteroscopy, 3d ultrasound or sonohysterogram documenting a normal uterine cavity within the last year; * normal cervical cytology/high risk human papillomavirus (hpv) testing per american college of obstetricians and gynecologists guidelines. exclusion criteria: * oligo or anovulation (spontaneous menses \> 39 days apart); * breastfeeding or pregnancy; * contraindication to pregnancy (i.e. an active, uncontrolled clinically significant medical condition or abnormality of the sexual organs determined by the provider); * known family history of major congenital anomalies; * moderate to severe current endometriosis (stage 3 or 4); * presence of a unilateral or bilateral hydrosalpinx that communicates with the uterus, that has not been ligated prior to treatment; * recurrent pregnancy loss (rpl) as defined by the american society of reproductive medicine (asrm) as two or more consecutive failed clinical pregnancies; * presence of a submucosal or intramural fibroid \> 4 cm which distorts the uterine cavity or are \> 5 cm in diameter; * untreated uterine pathology that could impair embryo implantation (i.e. scarring/asherman's syndrome or intra uterine polyps \> 1 cm in size); * type 1 or 2 diabetes mellitus based on american diabetes association (ada) criteria3; * uncontrolled adrenal or thyroid dysfunction; * history of conditions (i.e. toxic shock syndrome) that would contraindicate use of a vaginal progesterone product; * subjects with hepatic impairment (liver function tests \> 2x upper limit of normal); * subjects with renal impairment (estimated creatinine clearance \<60 ml/min/1.73 m2); * history of an active or treated autoimmune disease (i.e. systemic lupus erythematosus); * history of arterial disease (i.e. prior or active thrombophlebitis, thromboembolic disorder or known thrombophilia); * neoplasias (current) or history of neoplasia that may be responsive to progesterone; * high grade cervical dysplasia; * undiagnosed vaginal bleeding (i.e. at the time of screening); * use of donor eggs or plans to use a gestational carrier; * use of endometrial receptivity array (era) test to postpone or anticipate the embryo transfer (et) day; * use of epididymal, testicular , electro-ejaculated or chemotherapy exposed sperm; * known allergy to progesterone preparations or their excipients; * current dependence on alcohol, tobacco (must not be smoking/using tobacco x 2 months before the study) or drugs or psychotropic medications labeled as pregnancy categories d and x; * use of concomitant medications within 1 month previous the start of the fet cycle preparation up to gestational week 12 that might interfere with the study evaluation (use of insulin sensitizing agents, vaginal medications/preparations, any drugs for luteal support other than those specified in the protocol, aspirin, any hormonal treatment, with the exception of levothyroxine); * participation in a concurrent clinical trial or in another investigational drug trial within the past 2 months-

Keywords: frozen embryo transfer