How to Rescue Hormonal Replacement Frozen Embryo Transfer Cycle With Low Serum Progesterone? A Randomized Control Trial.
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 120
- Locations
- 2
- Primary Endpoint
- Clinical pregnancy rate
Study Overview
Brief Summary
Frozen embryo transfer (FET) is increasingly adopted strategy in modern IVF. Among the many factors that have contributed to such change, the pursuit of an ovarian hyperstimulation syndrome free clinic has been strongly required. Improvements in the vitrification and warming processes and the excellent cryo-survival rates have turned FET in our main tool for preventing this complication. Moreover, a freeze all strategy has proven to provide excellent or even better pregnancy rates (PRs), not only in high but also in normal responders.
While ART have rapidly evolved in the areas of embryo culture, vitrification and understanding of the embryo development, little progress has been achieved regarding endometrial preparation for FET. Undoubtedly, correct implantation requires a good quality embryo and a suitable decidualized endometrium. Artificial cycles require hormone replacement treatment (HRT) with estradiol and progesterone (P4). However, there is not a single standardized treatment described for optimal endometrial preparation and no protocol has proven superiority in terms of reproductive outcomes.(5, 6) Although artificial preparation is the most convenient method to schedule FET cycles, recent reports have highlighted a potentially detrimental effect of low P4 levels prior to FET on miscarriage and live birth rates (LBRs). These results have been observed both in homologous and oocyte recipient FET cycles(7, 8), but also in FET cycles of embryos that had undergone PGT for aneuploidies (PGT-A).(9) Additional P4 supplementation may be a way to improve reproductive outcomes in these patients.
Our open labelled randomized control study aims to investigate whether patients with low serum P4 levels the day before FET under standard HRT can benefit in terms of clinical and ongoing pregnancy and implantation rates from an individualized luteal phase support consisting in the addition of oral dydrogesterone supplementation or daily subcutaneous P4 injection.
Detailed Description
A randomized control trial which will be conducted at El-Shatby University Maternity Hospital and private two private ART centres in Alexandria, Egypt.
120 patients in which HRT-FET cycles with low serum progesterone levels will divided into two groups :
- Group A: 60 patients will be given oral 10 mg dydrogesterone (Duphaston®, Abbott) twice daily or,
- Group B: 60 patients will be given subcutaneous injection 25mg daily (Prolutex®, IBSA).
METHODS Investigation Basal hormonal profile before initiation of treatment, a basal hormonal profile will be performed in all patients (basal FSH, LH, and estradiol levels) Pelvic ultrasound using a transvaginal probe, to assess ovaries, tubes and document uterine size, shape and endometrial thickness.
Endometrial preparation:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 40 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Patient prepared for frozen blastocyst transfer.
- •Maternal age ranges from less than 40 years.
- •BMI < 35kg/m
- •Normal uterine cavity.
Exclusion Criteria
- •Uncorrected endometrial, uterine or pelvic pathology.
- •Recurrent implantation failure cases.
- •Patients suffering from recurrent miscarriages.
- •Male factor infertility due to azoospermia
Arms & Interventions
Oral dydrogesterone
60 patients in HRT frozen embryo transfer with low serum progesterone less than 10 ng/ml 24 hours before the embryo transfer will be given oral 10 mg dydrogesterone (Duphaston®, Abbott) twice daily
Intervention: Duphaston (Drug)
subcutaneous progesterone
60 patients in HRT frozen embryo transfer with low serum progesterone less than 10 ng/ml 24 hours before the embryo transfer will be subcutaneous injection 25mg daily (Prolutex®, IBSA).
Intervention: prolutex (Drug)
Outcomes
Primary Outcomes
Clinical pregnancy rate
Time Frame: at the 6 th weeks of pregnancy
percentage of cases in which observation of a gestational sac with fetal heart beat by transvaginal ultrasound at 6 weeks of pregnancy
Secondary Outcomes
- Serum progesterone level on the day of FET(on the day of embryo transfer(before transfer))
- Implantation rate(at the 6 th week of pregnancy)
- Ongoing pregnancy rate(At the 20 th week of gestation)
Investigators
Aly Hussein
Principal investigator
El Shatby University Hospital for Obstetrics and Gynecology