The Effectiveness and Safety of the Prolonged Down-regulation Protocol for Controlled Ovarian Hyperstimulation

Status

Status unknown

Phase

Phase 4

Enrollment

1,892 participants (estimated)

Sponsor

Peking University People's Hospital · Other

Design

Randomized · Single masking

Countries

Not stated

Start

1 Feb 2019 (estimated)

Primary completion

1 Sept 2020 (estimated)

Completion

31 Dec 2020 (estimated)

First posted

18 Jan 2019

Last update posted

18 Jan 2019

Conditions

Infertility, Female

Since the first "tube baby", Louise Brown, was born in the United Kingdom in 1978, many infertile couples have been benefitted from in vitro fertilization and embryo transfer (IVF-ET) and intracytoplasmic sperm injection (ICSI). Although a late starter, China is developing rapidly in ART and playing a more and more important role in the area of reproductive medicine. In spite of the continuous development in ART, so far, the overall success rate of IVF/ICSI is still hovering around 25-40%. There are many factors influencing the success rate of IVF/ICSI. Among them, an appropriate controlled ovarian hyperstimulation (COH) protocol is directly associated with the number of oocyte retrieved, as well as the number and quality of embryos, which exert an important influence on the success rate of IVF/ICSI. The luteal phase pituitary down-regulation protocol is one of the most widely used COH protocols in clinical practice, particularly in China. Though effective, it may lead to an increased incidence of ovarian hyperstimulation syndrome (OHSS), as well as a negative impact on endometrial receptivity. The coping strategy is to freeze all the embryos and transfer in the next cycle. Though avoiding the above mentioned adverse effects, such strategy increases the time to pregnancy (TTP) and therefore results in certain psychological and economic burdens for infertile couples. In recent years, some Chinese researches applied the early follicular full-dose down-regulation protocol that is always performed to women with endometriosis to a more general IVF/ICSI population and found a clinical pregnancy rate of 64% in the fresh embryo transfer cycle, much higher than that of the luteal phase down-regulation protocol. Furthermore, since this protocol decrease the risk of progesterone elevation on hCG day, it increases the fresh embryo transfer rate and shortens TTP. Given most studies regarding the effectiveness and safety of the early follicular phase full-dose down-regulation protocol are retrospective studies, the results may be biased by several confounding factors. Therefore, we would like to conduct a multicenter, randomized controlled trial to compare the pregnancy outcome and safety indicators between the early follicular phase full-dose down-regulation protocol and the luteal phase down-regulation protocol.

• Experimental

  early follicular phase down-regulation

  Patients have a injection of 3.75mg long-acting Triptorelin acetate (Dipherelin®, IPSEN, France) on the 1st-4th day of menstrual cycle. If complete pituitary down-regulation is achieved after 28-42 days, exogenous gonadotropins will be given according to the participants' BMI. The physician will monitor the follicular growth and adjust the dose of exogenous gonadotropins accordingly. When the desired follicle size is reached, human chorionic gonadotropin will be administered. Oocyte retrieval will be performed 36-38 hours after pre-ovulatory hCG injection transvaginally under ultrasound monitoring. Oocyte retrieved will be cultured in vitro for 3-6h before being fertilized via IVF or ICSI. Two top-quality Day 3 cleavage embryos will be transferred 72h after retrieval.

• Active comparator

  luteal phase down-regulation

  Patients have a injection 0.1mg short-acting Triptorelin acetate (Decapeptyl®, Ferring, Germany) every day, 10-12 days before the next menstrual cycle. If complete pituitary down-regulation is achieved after 14-21 days, exogenous gonadotropins will be given according to the participants' BMI. The physician will monitor the follicular growth and the serum hormone level and adjust the dose of exogenous gonadotropins accordingly. When the desired follicle size is reached, human chorionic gonadotropin will be administered. Oocyte retrieval will be performed 36-38 hours later under ultrasound monitoring. Oocyte retrieved will be cultured in vitro for 3-6h before being fertilized via IVF or ICSI. Two top-quality Day 3 cleavage embryos will be transferred 72h after retrieval.

1. live birth rate per transferred cycle

   Time frame · 28 weeks of gestation

   Registry description

   the number of live births (after 28 gestational week) divided by the number of transferred fresh cycles ×100%;

No study cites this trial.