Overview

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

Status:
Unknown status
Trial end date:
2020-12-31
Target enrollment:
0
Participant gender:
Female
Summary
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.
Phase:
Phase 4
Accepts Healthy Volunteers?
Accepts Healthy Volunteers
Details
Lead Sponsor:
Peking University People's Hospital
Collaborators:
First Affiliated Hospital of Guangxi Medical University
First Affiliated Hospital of Wenzhou Medical University
Guangxi Maternal and Child Health Hospital
Henan Provincial Hospital
Henan Provincial People's Hospital
Jiangxi Maternal and Child Health Hospital
Peking University First Hospital
Second Affiliated Hospital of Wenzhou Medical University
Second Affiliated Hospital of Zhengzhou University
Shanxi Provincial Maternity and Children's Hospital
The First Affiliated Hospital of Zhengzhou University
The Second Hospital of Hebei Medical University
West China Hospital
Xinjiang Jiayin Hospital
Yinchuan Municipal Maternal and Child Health Hospital
Treatments:
Chorionic Gonadotropin
Follicle Stimulating Hormone
Hormones
Triptorelin Pamoate
Criteria
Inclusion Criteria:

1. Women aged between 20 to 35 years old and with a history of infertility (fail to get
pregnant after over one year's regular, unprotected sex), who receive IVF/ICSI for one
of the following reasons:

① Tubal factor: e.g. peritubal adhesions, tubal obstruction, etc.. Patients with
hydrosalpinx can be enrolled after salpingectomy or tubal ligation;

② Male factor: e.g. oligospermia, asthenozoospermia, teratozoospermia, etc.;

③ Unexplained infertility: patients with a history of infertility more than 1 year but
with no specific cause for infertility (ovulation, tubal, endometrial and male
factor), or still not get pregnant after the above-mentioned causes being removed.

2. Women with a normal ovarian reserve according to: ①basal steroid hormone on day 2-4 of
menstrual cycle: basal FSH≤10mIU/ml, estradiol (E2) <50pg/ml;②1.5 hormone (AMH)<4.0;③8≤antral follicle count (AFC) ≤15;

3. First IVF/ICSI cycle;

4. BMI≥18 and ≤25kg/m2;

5. Informed consent

Exclusion Criteria:

1. Women with a negative reproductive history, including a history of:

① recurrent miscarriage: women with twice and more than twice spontaneous miscarriage,
missed abortion, biochemical pregnancies, etc.;

② fetal malformation or chromosomal abnormalities;

③ intrauterine death.

2. Women with a history of one side adnexectomy;

3. Women with a poor ovarian response or diminished ovarian reserve (based on Bologna'
criteria);

4. Women with ovulation dysfunction;

5. Women with PCOS (based on Rotterdam's criteria);

6. Women with endometriosis;

7. Women with the following uterine abnormalities: uterine malformation (unicornuate
uterus, uterus bicornis, uterus duplex, mediastinum uterus), adenomyosis, submucosa
myoma, intrauterine adhesion;

8. Chromosomal abnormality for either or both of the couple;

9. Women with contraindications for ART or pregnancy: uncontrolled diabetes mellitus,
cardiac disease, undiagnosed liver and/or renal function, vaginal bleeding, suspected
or a past history of cervical cancer, endometrial cancer, breast cancer, and a history
of deep venous thrombosis, pulmonary embolism, stroke, etc.;

10. Women who are enrolled in other clinical trials.