Clinical trial NCT01841528: Live Birth After Fresh Embryo Transfer Vs Frozen-thawed Embryo Transfer in Women With Polycystic Ovary Syndrome
Official title: Live Birth After Fresh Embryo Transfer vs Elective Embryo Cryopreservation/Frozen Embryo Transfer in Women With Polycystic Ovary Syndrome Undergoing IVF: A Multi-center Prospective Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Polycystic Ovary Syndrome
Infertility
Keywords: Polycystic Ovary Syndrome
Infertility
In-vitro fertilization
fresh embryo transfer
frozen-thawed embryo transfer
Lead sponsor: Shandong University
Sponsor class: OTHER
Collaborators: name: The First Affiliated Hospital with Nanjing Medical University
name: Sixth Affiliated Hospital, Sun Yat-sen University
name: Anhui Medical University
name: RenJi Hospital
name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: LanZhou University
name: Guangxi provincial maternal and chidren's hospital
name: Renmin Hospital of Wuhan University
name: Yantai Yuhuangding Hospital
name: Jiangxi Maternal and Child Health Hospital
name: Sir Run Run Shaw Hospital
name: Shanxi Provincial Maternity and Children's Hospital
name: Reproductive Medicine Center in Shenyang City
First posted: 2013-04-26
Enrollment: 1180
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 34
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: live birth rate
timeFrame: 10 months for group A, 12 months for group B
Secondary outcomes:
measure: Ovarian hyperstimulation syndrome (OHSS) incidence
timeFrame: 2 months in maximum estimated
measure: clinical pregnancy rate
timeFrame: 35 days after embryo transfer
measure: Pregnancy Loss rate
timeFrame: 28 weeks gestation in maximum
measure: ectopic pregnancy rate
timeFrame: 7~8 weeks gestation
measure: singleton live birth rate
timeFrame: 10 months for group A, 12 months for group B
measure: pregnancy complication rate
timeFrame: 10 months for group A, 12 months for group B
measure: Congenital Anomalies rate
timeFrame: 10 months for group A, 12 months for group B
measure: neonatal complication rate
timeFrame: within one month after labor
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Lanzhou
country: China
facility: The First Affiliated Hospital of Lanzhou University
state: Gansu
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: The sixth Affiliated Hospital of Sun Yat-Sen University
state: Guangdong
city: Nanning
country: China
facility: Guangxi Maternal and Child Health Hospital
state: Guangxi
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Maternal and Child Health Hospital
state: Jiangxi
city: Shenyang
country: China
facility: Reproductive Medicine Center in Shenyang City
state: Liaoning
city: Jinan
country: China
facility: Reproductive medical hospital affiliated to Shandong University
state: Shandong
city: Yantai
country: China
facility: Yuhuangding Hospital in Yantai
state: Shandong
city: Shanghai
country: China
facility: Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Xi'an
country: China
facility: Shanxi Provincial Maternity and Children's Hospital
state: Shanxi
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital
state: Zhejiang
Study officials:
affiliation: Repreductive medical hospital affiliated to Shandong University
name: Zi-jiang Chen, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Shi Y, Wei D, Liang X, Sun Y, Liu J, Cao Y, Zhang B, Legro RS, Zhang H, Chen ZJ. Live birth after fresh embryo transfer vs elective embryo cryopreservation/frozen embryo transfer in women with polycystic ovary syndrome undergoing IVF (FreFro-PCOS): study protocol for a multicenter, prospective, randomized controlled clinical trial. Trials. 2014 May 2;15:154. doi: 10.1186/1745-6215-15-154.