Human Menopausal Gonadotropin Research in Infertility Assessing Cumulative Live Birth With Frozen Embryo Transfer.

A Multicenter, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Efficacy and Safety of a Human Menopausal Gonadotropin in the Development of Multiple Follicles, Pregnancy, and Cumulative Live Birth as Part of an Assisted Reproductive Technology (ART) Cycle.

The goal of this multicenter, randomized, placebo-controlled, double-blind clinical trial is toto evaluate the efficacy and safety of a human menopausal gonadotropin (hMG) in the development of multiple follicles, pregnancy, and cumulative live birth as part of an Assisted Reproductive Technology (ART) cycle in in women with a diagnosis of infertility.

Inclusion Criteria:

• Pre-menopausal women aged 18-42 years old at the time of consent.
• BMI ≥18 and <38 kg/m² at the time of consent.
• Menstrual cycles between 21-35 days.
• Normal mammogram or breast ultrasound if patient is >40 or if participant is younger as indicated by physician recommendation, within 2 years of screening.
• Anti-Müllerian hormone (AMH) >1.2 ng/ml within 6 months of screening.
• If donor sperm is used, 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.
• Transvaginal ultrasound (TVUS) documenting presence and adequate visualization of both ovaries without ovarian enlargement, normal adnexa, and both ovaries accessible for oocyte retrieval at screening or within 6 months of screening.
• Valid medical indication for in vitro fertilization (IVF) treatment and subsequent embryo transfer (i.e. history of infertility according to current American Society of Reproductive Medicine (ASRM) definition, single women or same-sex couples) with the intention to achieve pregnancy within 12 months of the first stimulation cycle.
• Hysterosalpingography, hysteroscopy or saline infusion sonography, documenting a normal uterine cavity (i.e. no müllerian duct anomaly, uterine fibroids, endometrial polyps, intrauterine adhesions, adenomyosis) at screening or within 1 year prior to screening.
• Normal cervical cytology/high risk human papillomavirus (HPV) testing per American College of Obstetrician/Obstetrician Gynecologist (OB/GYN) (ACOG) guidelines.
• Negative serum hepatitis B surface antigen, hepatitis C antibody, human immunodeficiency virus (HIV) antibody tests at screening.
• Absence of hydrosalpinx confirmed by hysterosalpingogram (HSG), sonohysterogram, laparoscopy, or other appropriate imaging within the past 12 months.
• Willing to undergo up to two ovarian stimulation cycles prior to frozen embryo transfer.
• Willing to self-administer study medications.
• Willing to have trophectoderm biopsy of all blastocyst stage embryos.
• Willing to accept transfer of one euploid embryo.
• Willing to vitrify and warm embryo(s) with intention to have a Frozen Embryo Transfer (FET).
• Willing and able to comply with the protocol and schedule of events for the duration of the study as well as providing delivery data and neonatal health data.

Exclusion Criteria:

• Persistent (for >1 cycle), clinically relevant (per PI discretion) ovarian cystic lesion (≥20 mm), including ovarian endometrioma or dermoid cyst.
• Participants with hepatic impairment (liver function tests > 2x upper limit of normal). Participants with renal impairment (estimated creatinine clearance <60 mL/min/1.73 m2).
• Uncontrolled adrenal, thyroid dysfunction or uncontrolled diabetes (HbA1C >7% within 3 months from screening).
• Greater than one IVF cycle canceled due to inability to meet ovulation trigger criteria (i.e. at least 2-3 follicles reach ≥18 mm.).
• History of recurrent implantation failure (RIF), defined according to the Lugano Consensus as the absence of implantation after transfer of ≥4 good-quality embryos in ≥3 embryo transfer (ET) cycles in women under the age of 40, using autologous oocytes.
• Recurrent pregnancy loss (RPL) is defined by two or more miscarriages; that is clinical pregnancies with the same partner and documented by ultrasonography or histopathological examination.
• Known history of anovulation.
• Antral Follicle Count (AFC) <5 at screening.
• One or more dominant follicles (≥11 mm) observed on TVUS prior to randomization on stimulation day 1 with evidence of functional activity defined as serum Estradiol level >100 pg/ml.
• Past or current history of an estrogen dependent malignancy
• Untreated atypical endometrial hyperplasia
• Any contraindication to the use of oral contraceptives
• History of OHSS.
• Morphological sperm evidence of globozoospermia or prior failed oocyte fertilization in previous IVF cycle.
• The use of donor sperm back up or rescue for fertilization of oocytes.
• Use of calcium ionophore or treatment of sperm with methyl xanthines.
• The need for surgically retrieved sperm (i.e. testicular sperm extraction [TESE], Percutaneous Epididymal Sperm Aspiration [PESA]).
• Use of any investigational drug throughout the study, or within 3 months before screening or 5 half-lives whichever is longer.
• Use of any concomitant medications that would interfere with the study drug and with the evaluation of the study (e.g., hormonal medications or other medications affecting reproductive function), as determined by the investigator, unless permitted by the protocol or meeting required washout criteria.
• Current use or dependence on psychotropic medications that are contraindicated during pregnancy or have known or suspected fetal risk, unless the Investigator determines that the potential benefit outweighs the risk.
• Required chronic use of non-steroidal anti-inflammatory drugs during cycle.
• Treatment with clomiphene citrate, metformin, cabergoline, gonadotropins, or GnRH analogs within 1 month prior to randomization.
• Pregnancy, lactation, or contraindication to gonadotropins.
• Known thrombophilia or history of blood clots unless fully evaluated and cleared by a hematologist and receiving appropriate prophylaxis.
• Known abnormal karyotype in the patient or her partner that is considered clinically significant, such as numerical or structural chromosomal abnormalities (e.g., translocations, inversions, aneuploidies) known to impair fertility, increase risk of miscarriage, or result in genetic disorders in offspring.
• Current tobacco or marijuana user.
• Current or past (last 12 months) abuse of alcohol or drugs.
• Current use of dietary supplements containing high dose of biotin (>300µg), if prior use washout period of 1 week prior to randomization.
• No use of bioidentical hormones during stimulation or up to three months prior to start of stimulation. If prior use: washout period of three months prior to being randomized.
• A history of chemotherapy or radiotherapy.
• Undiagnosed uterine bleeding.
• Tumors of the ovary, breast, adrenal gland, pituitary, or hypothalamus; malformation of sexual organs incompatible with pregnancy.
• Known active pelvic inflammatory disease.
• Current, untreated submucosal fibroids or Intramural fibroids ≥5 cm or otherwise clinically relevant pathology that could impair embryo implantation or pregnancy continuation.
• The presence of severe endometriosis (ASRM stage 3 or stage 4) confirmed by laparoscopy, Magnetic Resonance Imaging (MRI), or pelvic ultrasound.
• Concomitant participation in another study protocol.
• Couples identified as carriers of the same autosomal recessive genetic condition associated with serious health outcomes in offspring will be excluded from the trial.
• Planned use of a gestational carrier.