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

Infertility Clinical Trial

— FreFro-PCOS  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01841528
• Other study ID #: SDUIVF001
• Status: Active, not recruiting
• Phase: N/A
• First received: April 18, 2013
• Last updated: April 14, 2014
• Start date: June 2013
• Est. completion date: June 2015

Study information

• Verified date: April 2014
• Source: Shandong University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1180
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 34 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infertility
• Polycystic Ovary Syndrome
• Syndrome

Intervention

Other:
• fresh embryo transfer
rFSH/GnRH antagonist will be administered for ovarian stimulation. Oocyte pick-up will be performed when at least two follicles =18mm. 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 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.
• frozen-thawed embryo transfer
rFSH/GnRH antagonist will be administered for ovarian stimulation. Oocyte pick-up will be performed when at least two follicles =18mm. 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 HRT (hormone replacement therapy) prepared endometrium. Luteal phase support will last 2 weeks for all subjects in this group. Two weeks after embryo transfer, serum 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.

Locations

Country	Name	City	State
China	Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University	Guangzhou	Guangdong
China	The sixth Affiliated Hospital of Sun Yat-Sen University	Guangzhou	Guangdong
China	Sir Run Run Shaw Hospital	Hangzhou	Zhejiang
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	Reproductive medical hospital affiliated to Shandong University	Jinan	Shandong
China	The First Affiliated Hospital of Lanzhou University	Lanzhou	Gansu
China	Jiangxi Maternal and Child Health Hospital	Nanchang	Jiangxi
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Guangxi Maternal and Child Health Hospital	Nanning	Guangxi
China	Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	Reproductive Medicine Center in Shenyang City	Shenyang	Liaoning
China	Renmin Hospital of Wuhan University	Wuhan	Hubei
China	Shanxi Provincial Maternity and Children's Hospital	Xi'an	Shanxi
China	Yuhuangding Hospital in Yantai	Yantai	Shandong

Sponsors (14)

Lead Sponsor

Collaborator

Zi-jiang Chen

Anhui Medical University, Guangxi provincial maternal and chidren's hospital, Jiangxi Maternal and Child Health Hospital, LanZhou University, RenJi Hospital, Renmin Hospital of Wuhan University, Reproductive Medicine Center in Shenyang City, Shanxi Provincial Maternity and Children's Hospital, Sir Run Run Shaw Hospital, Sixth Affiliated Hospital, Sun Yat-sen University, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, The First Affiliated Hospital with Nanjing Medical University, Yantai Yuhuangding Hospital

Country where clinical trial is conducted

China, 

References & Publications (1)

[1] Boomsma CM, Eijkemans MJ, Hughes EG, et al. A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome. Hum Reprod Update 12:673-83,2006. [2] Hayashi M, Nakai A, Satoh S, et al. Adverse obstetric and perinatal outcomes of singleton pregnancies may be related to maternal factors associated with infertility rather than the type of assisted reproductive technology procedure used. Fertil Steril 98:922-928,2012. [3] Chen XK, Wen SW, Bottomley J, et al. In vitro fertilization is associated with an increased risk for preeclampsia. Hypertens Pregnancy 28:1-12,2009. [4] Thomopoulos C, Tsioufis C, Michalopoulou H, et al. Assisted reproductive technology and pregnancy-related hypertensive complications: a systematic review. J Hum Hypertens 27:148-57,2013. [5] Haavaldsen C, Tanbo T, Eskild A. Placental weight in singleton pregnancies with and without assisted reproductive technology: a population study of 536,567 pregnancies. Hum Reprod 27:576-82,2012. [6] Maheshwari A, Pandey S, Shetty A, et al. Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of frozen thawed versus fresh embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis. Fertil Steril 98:368-77 e1-9,2012. [7] Kalra SK, Ratcliffe SJ, Coutifaris C, et al. Ovarian stimulation and low birth weight in newborns conceived through in vitro fertilization. Obstet Gynecol 118:863-871,2011.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	live birth rate	This will be based on the outcome of either the fresh embryo transfer after ovarian stimulation (Group A) or the outcome of the first frozen embryo transfer cycle (Group B) as will all other secondary outcomes.	10 months for group A, 12 months for group B	No
Secondary	Ovarian hyperstimulation syndrome (OHSS) incidence		2 months in maximum estimated	Yes
Secondary	clinical pregnancy rate	This will be based on the visualization of a intrauterine gestational sac by ultrasound.	35 days after embryo transfer	No
Secondary	Pregnancy Loss rate	Loss of pregnancy will be defined by any positive pregnancy test that does not result in a live birth and will be tracked.	28 weeks gestation in maximum	Yes
Secondary	ectopic pregnancy rate		7~8 weeks gestation	Yes
Secondary	singleton live birth rate		10 months for group A, 12 months for group B	No
Secondary	pregnancy complication rate	Complications of pregnancy including gestational hypertension, diabetes, preterm labor, disorders of placentation will be collected in all patients with ongoing clinical pregnancies.	10 months for group A, 12 months for group B	Yes
Secondary	Congenital Anomalies rate	We will collect all recognized fetal and infant anomalies that occur within the trial.	10 months for group A, 12 months for group B	Yes
Secondary	neonatal complication rate	We will collect complications that occur in the neonate including admission to the neonatal intensive care unit (NICU), hospitalization, etc.	within one month after labor	Yes