A study of hormones in infertile women undergoing IVF

Phase 3

Completed

• Conditions: Female infertility, unspecified,

• Registration Number: CTRI/2019/10/021801
• Lead Sponsor: Sanzyme P Ltd

Brief Summary

A prospective, randomized, open-label, controlled, clinical study to compare the clinical efficacy and tolerability of two highly purified human menopausal gonadotropin preparations administered subcutaneously in women undergoing in vitro fertilization.



Primary Objective:

To evaluate the clinical efficacy of two different highly purified (HP) human menopausal gonadotropin (hMG) preparations (Gynogen® HP and Menopur®), when administered subcutaneously (s.c.) to female patients undergoing controlled ovarian stimulation (COS) for in vitro fertilization (IVF) on oocyte maturation and retrieval.



Secondary Objective:

To evaluate additional clinical efficacy, tolerability, and safety of two different HP-hMG preparations (Gynogen® HP and Menopur®), when administered s.c. to female patients undergoing COS for IVF.



This is a multicentre, prospective, randomized, open-label, controlled, parallel-group trial.



The purpose of this non-inferiority study is to compare the clinical efficacy and general tolerability of two different HP-hMG preparations (Gynogen®HP; Sanzyme Pvt. Ltd. and Menopur®, Ferring Pharmaceuticals, Inc.) when

administered s.c. to female patients undergoing COS for IVF. Eligible patients will be randomized in a 1:1 ratio to receive either the Test hMG (Gynogen® HP) or the Reference hMG (Menopur®) products.

Enrolled patients will undergo down-regulation using a standard gonadotropin-releasing hormone (GnRH) agonist long regimen with leuprolide. Leuprolide acetate 0.5 mg subcutaneously will be administered starting from Day 21 of the previous menstrual cycle (C0). After the downregulation, hMG administration will be initiated at 150-225 IU daily starting from Day 1/2 of the current menstrual cycle (C1). This dose will be maintained for approximately first 4-5 days. The patient will also continue to receive GnRH agonist simultaneously; the dose of leuprolide acetate will be decreased to 0.25 mg starting on Day 3 of Cycle 1 and continued daily until the day of hCG administration. Thereafter, hMG dose adjustments will be allowed depending on the ovarian response monitored by means of serum E2 levels and transvaginal ultrasonography (TVUS). Patients will be routinely monitored via TVUS and hormonal profiling of follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2, and progesterone (P4) levels.



The hMG administration (+ GnRH agonist) will be continued until at least two follicles ≥14 to 16 mm in diameter are observed on TVUS and serum E2 levels are appropriate for the total number of developing follicles, or as per

Investigator’s clinical judgement. Patients fulfilling this criterion will be administered 5000-10,000 IU hCG (Pubergen® only; will be provided as part of the study drugs supplies) injection.

After 34-36 hours of hCG injection, the mature oocytes will be retrieved and artificially fertilized.

Luteal phase support will be performed as per the site’s routine practice.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-11-18
• Study Completion: 2021-04-05
• Last Update Posted: 2021-09-21

Recruitment & Eligibility

• Status: Completed
• Sex: Female
• Target Recruitment: 144

Inclusion Criteria

• 1. Women undergoing COS for their first or second cycle of IVF with or without intracytoplasmic sperm injection (ICSI) with following characteristics:.
• Age > 21 and ≤ 40 years.
• Ability to provide written informed consent voluntarily for study participation, along with consent by partner or spouse.
• Body mass index between 18.5 and 30 kg/m2.
• Basal FSH, LH, E2, P4 at luteal phase and prolactin (PRL) levels within normal range.
• Normal antral follicle count (AFC) (6 to 10).
• Normal ovulatory cycles of 21 to 35 days inclusive 2. TVUS documenting the presence of both ovaries, without evidence of abnormality (e.g., no endometrioma) and normal adnexa (e.g., no hydrosalpinx) within 6 months prior to randomization. 3. Normal or clinically insignificant haematology and blood chemistry values. 4. Husband/male partner with normal sperm motility and sperm count.

Exclusion Criteria

• History of more than 2 unsuccessful induction cycles with hMG or hCG regimen or intolerability to regimens requiring discontinuation.
• Primary or secondary ovarian failure or women known as poor responders.
• Patient with a history of ≥3 miscarriages.
• Presence of only one ovary or ovarian abnormality or ovarian cysts >10 mm in size for >1 cycle or ovarian endometrioma.
• Patients with polycystic ovary syndrome.
• Hydrosalpinx that have not been surgically removed or ligated.
• Stage III or IV endometriosis.
• Abnormality on endometrial biopsy.
• Patients with submucosal fibroids ≥5 cm or any other clinically relevant pathology, which could impair embryo implantation or pregnancy continuation 10.
• Tubal pathologies or history of ectopic pregnancy.
• Prior history of OHSS.
• Allergy, intolerance, or hypersensitivity to the study medication or its excipients.
• Abnormal bleeding of undetermined origin.
• Any history of malignancy or significant systemic disease (cardiovascular, gastrointestinal, pulmonary, neurological, or autoimmune), endocrine or metabolic abnormalities (pituitary,thyroid, adrenal, pancreas, hepatic or renal), or any active condition requiring treatment, which, according to the investigator, might interfere with the study.
• Metabolic disorders such as type I or type II diabetes mellitus.
• Tumours and malformation of sexual organs incompatible with pregnancy.
• Hyperprolactinaemia.
• Women with severe infections of the reproductive system such as tuberculosis, sexually transmitted diseases, etc.
• Known positive history of human immunodeficiency virus (HIV), hepatitis B or C, or syphilis.
• Abnormality in the partner’s semen based on semen analysis.
• Use of concomitant medication that might interfere with ovulation (e.g., neuroleptics) or study evaluations, or concomitant medications with known or suspected teratogenic agents (e.g., Food and Drug Administration Class X drugs).
• Pregnancy, lactation, or contraindication to pregnancy.
• Current or past (last 12 months) abuse of alcohol or drugs; women who smoke or have stopped smoking in the past 3 months.
• Participation in a concurrent clinical trial or in another trial within the past 6 months.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Total number of mature oocytes retrieved	34 to 36 hours after human | chorionic gonadotropin (hCG) administration

Secondary Outcome Measures

Name	Time	Method
- Drug utilization in terms of total dose of hMG (IU, total number of vials, and vials per day)	- Stimulation duration in terms of number of days of hMG stimulation (from stimulation onset until hCG injection)

Trial Locations

Locations (5)

Ajanta Hospital and IVF Centre; 🇮🇳 Lucknow, UTTAR PRADESH, India

Bavishi Fertility Institute; 🇮🇳 Ahmadabad, GUJARAT, India

GP Shekawati Hospital and Research Centre; 🇮🇳 Jaipur, RAJASTHAN, India

Milann IVF Centre; 🇮🇳 Bangalore, KARNATAKA, India

Sri Ramachandra Insitute of Higher Education and Research; 🇮🇳 Chennai, TAMIL NADU, India

Ajanta Hospital and IVF Centre

🇮🇳Lucknow, UTTAR PRADESH, India

Dr Gita Khanna

Principal investigator

9335913046

ivfajanta@gmail.com