Live Birth After Fresh Embryo Transfer Vs Frozen-thawed Embryo Transfer in Women With Polycystic Ovary Syndrome (FreFro-PCOS)

Zi-jiang Chen

Status: Unknown

Conditions: Infertility; Polycystic Ovary Syndrome

Treatments: Other: fresh embryo transfer; Other: frozen-thawed embryo transfer

Study type: Interventional

Funder types: Other

Identifiers

NCT01841528

SDUIVF001

Details and patient eligibility

About

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of childbearing age. However, the optimal infertility treatment for PCOS patients is still a matter of controversy. Despite producing more follicles and more oocytes than other women undergoing controlled ovarian hyperstimulation during an IVF cycle, women with PCOS have comparable or lower pregnancy rates. Additionally women with PCOS patients undergoing IVF have a higher risk of developing ovarian hyperstimulation syndrome (OHSS), which may be aggravated by pregnancy after an embryo transfer in a fresh cycle. Further women with PCOS are thought to have higher rates of later pregnancy complications including spontaneous abortion, pre-eclampsia, and preterm labor that may be related to impaired implantation in the superovulated endometrium. We propose a randomized clinical trial of elective embryo cryopreservation followed by a programmed cycle of endometrial preparation and frozen embryo transfer (FET) compared to fresh embryo transfer in women with PCOS undergoing in vitro fertilization (IVF).

Full description

This will be a multi-center, prospective, randomized (1:1 ratio)clinical trial of frozen-thawed embryo transfer vs. fresh embryo transfer after a uniform gonadotropin-releasing hormone (GnRH) antagonist protocol in infertile PCOS patients receiving IVF therapy. Qualified 1180 patients are randomized into either of two groups: group A will undergo fresh embryo transfer (590 cases), Group B will undergo elective cryopreservation of all embryos followed by transfer of thawed embryos to a programmed endometrium (590 cases). All of the participants will receive recombinant follicule stimulating hormone (rFSH)/GnRH antagonist protocol for ovarian stimulation and standardized luteal phase support.

The target population will be infertile PCOS patients aged between 20 and 35 years, diagnosed by the Chinese PCOS Criteria(i.e. menstrual disorders PLUS either one of the remaining two criteria, hyperandrogenism or polycystic ovaries on ultrasound, with exclusion of secondary causes of hyperandrogenism and ovulation dysfunction). And subjects will be those who are undergoing their first IVF or intracytoplasmatic sperm injection (ICSI) cycle without other known factors interfere reproductive or metabolic functions.

The randomization will take place at the oocyte pick-up day by an on-line randomization system.

The pregnancy test results, pregnancy complications, congenital anomalies neonatal complications will be followed up by checking medical records and telephone calls.

Enrollment: 1,180 estimated patients

Sex: Female

Ages: 20 to 34 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Women diagnosed as PCOS according to Chinese PCOS diagnosis criteria;

• Women who have ≥1 years history of infertility;

• Women aged ≥20 and <35 years old;

• Women with body weight ≥40kg;

• Women who have at least one of the following indications for IVF or ICSI:

  1. Ovulation dysfunction and failed to become pregnant from ovulation induction treatment;
  2. Tubal factors: unilateral or bilateral tubal obstruction, adhesion, unilateral or bilateral Salpingectomy or tubal ligation;
  3. Male factors: oligoasthenozoospermia, obstructive azoospermia;

• Women who are undergoing their first cycle of IVF or ICSI;

• Women who retrieved oocytes number > 3;

• Women who are capable of giving informed consent.

Exclusion criteria

• Women who underwent unilateral ovariectomy;
• Women diagnosed as uterus abnormality: malformed uterus (uterus unicorns, septate uterus, duplex uterus, uterus bicomis), adenomyosis, submucous myoma, intrauterine adhesion;
• Women or their partner with abnormal chromosome karyotype including chromosome polymorphism;
• Women who have experienced recurrent spontaneous abortion (including biochemical pregnancy abortion) more than 2 times;
• Women with medical condition that represent contraindication to assisted reproductive technology and/or pregnancy;
• Women who has developed severe OHSS before oocyte pick-up day;
• Women with retrieved oocytes number ≤3;
• Women who are unable to comply with the study procedures.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,180 participants in 2 patient groups

fresh embryo transfer group

Experimental group

Description:

rFSH/GnRH antagonist will be administered for ovarian stimulation. Two fresh embryos will be transferred at Day 3. Luteal phase support will last 2 weeks for all subjects in this group. Two weeks after embryo transfer, serum human chorionic gonadotropin (HCG) will be measured to determine pregnant or not. If biochemical pregnancy is achieved, luteal phase support will be continued to 10 weeks gestation. Pregnancy complications and final outcome will be followed up till 6 weeks after delivery.

Treatment:

Other: fresh embryo transfer

frozen-thawed embryo transfer group

Experimental group

Description:

rFSH/GnRH antagonist will be administered for ovarian stimulation. All embryos will be vitrified in fresh cycle, and at least 2 embryos should be frozen at Day 3. Two months later, two thawed Day 3 embryos will be transferred with hormone replacement therapy (HRT) prepared endometrium. Luteal phase support will last 2 weeks for all subjects in this group. Two weeks after embryo transfer, serum human chorionic gonadotropin (HCG) will be measured to determine pregnant or not. If biochemical pregnancy is achieved, luteal phase support will be continued to 10 weeks gestation. Pregnancy complications and final outcome will be followed up till 6 weeks after delivery.

Treatment:

Other: frozen-thawed embryo transfer