Study Title A Real-world study to evaluate the Reproductive outcomes and Safety Profile in patients treated with Dydrogesterone for Luteal Phase Support in ART: A Prospective Observational Study

Background Patients with threatening or recurrent miscarriages are given progestogens in the first trimester to help the pregnancy progress, although this treatment is controversial. Micronized Progesterone (P4) supplementation is safe and effective; however, most patients find the vaginal or subcutaneous injection unreliable. [1] Dydrogesterone (DG) is a retroprogesterone, it has replaced micronized P4 in clinical practice with high patient compliance. Similarly, for Luteal phase support during the Assisted Reproductive Techniques (ART) the usual treatment provided is Progesterone supplementation or human chorionic gonadotropin (hCG). However, these are associated with risk of ovarian hyperstimulation syndrome. Dydrogesterone is an established oral retro progesterone is being used for treatment of threatened and recurrent miscarriage (associated with proven progesterone deficiency), and infertility due to luteal phase insufficiency since 1960. Recent clinical trials have supported the use of Dydrogesterone which is proven to be as effective as Micronized Vaginal Progesterone (P4), hence the doctors are using it routinely for Luteal Phase Support during the Assisted reproductive techniques (ART) [2] Dydrogesterone, is a powerful oral progesterone receptor agonist discovered in the 1950s, has been widely used since the 1960s for menstrual problems like premenstrual syndrome, menstrual cycle irregularity, endometriosis, threatening and recurrent miscarriages, and postmenopausal hormone therapy. Unlike other progestins, dydrogesterone and its principal active metabolite, 20α hydroxy-dydrogesterone, have no clinically meaningful agonistic or antagonistic activity on the androgen, oestrogen, and glucocorticoid receptors and only moderate anti mineralocorticoid characteristics [3]

Due to Dydrogesterone’s excellent selectivity for the progesterone receptor, it can be administered at levels 10–20 times lower than micronized progesterone. In addition, unlike other forms of progesterone, the primary metabolite of dydrogesterone, 20-dihydro-dydrogesterone, has the same progestogenic selectivity as the parent molecule, hence decreasing side effects. Dydrogesterone has been shown to have a good safety profile with a low incidence of maternal complications. It also seems to be as well tolerated as vaginal progesterone in safety analyses from studies assessing Dydrogesterone use in luteal phase support (LPS) during in vitro fertilization (IVF) as well as those investigating Dydrogesterone use in threatened and recurrent miscarriage. An RCT comparing Dydrogesterone versus vaginal progesterone gel in luteal phase support confirmed that patients receiving progesterone gel experienced a higher incidence of vaginal irritation and discharge, vaginal bleeding, and interference with sexual activity compared with patients receiving Dydrogesterone [4] There are no sufficient data of larger real-world evidence-based studies conducted in the Indian setting. Hence this real-world, multicenter, prospective, observational study has been planned to evaluate the effectiveness of Dydrogesterone and patient outcomes in Luteal Phase Support treatment.

Study Objective

Primary objective:

To evaluate the Reproductive outcomes in patients treated with Dydrogesterone for Luteal Phase Support.

Secondary Objective:

To evaluate the safety in IVF patients treated with Dydrogesterone.

Study Design

A Prospective, Multicentric, Observational, Real-world Evidence Study

Study Phase

Real-world, Observational Study

Study Sites

The study is planned to be conducted at 50 sites and 9 locations across India

Sample size

The required sample size for recruitment for the study would be 431 patients. However, we plan to enrol 1000 female patients undergoing LPS treatment from up to 50 clinical study sites in India to meet the required sample size number.

Study Patients

Inclusion Criteria:

Patients meeting with following criteria to be included in the study:

Female patients of age ≥ 21 years.

Patients who are legally married

Patients who require Luteal Phase Support during the Assisted reproductive techniques (ART)

Patients who are prescribed Dydrogesterone as part of routine clinical practice as determined by the Investigator.

Patients or their legally representatives who are willing provide written informed consent to participate in the study and are willing to adhere to the study procedures as per the protocol.

Exclusion Criteria:

Patients meeting with following criteria to be excluded from the study:

Patients with known severe liver or severe kidney or liver dysfunction at the time of initiation of trial