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

NCT01841528 | Unknown DMC

• 1 other identifier: SDUIVF001
• Study Type: interventional
• Target: 1,180
• Locations: 1 country
• Sites: 14

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).

Conditions

Polycystic Ovary Syndrome; Infertility

Keywords

Polycystic Ovary Syndrome; Infertility; In-vitro fertilization; fresh embryo transfer; frozen-thawed embryo transfer

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (8)

• Ovarian hyperstimulation syndrome (OHSS) incidence

  2 months in maximum estimated

• clinical pregnancy rate

  35 days after embryo transfer

• Pregnancy Loss rate

  28 weeks gestation in maximum

• ectopic pregnancy rate

  7~8 weeks gestation

• singleton live birth rate

  10 months for group A, 12 months for group B

Study Arms (2)

fresh embryo transfer group

EXPERIMENTAL

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.

Other: fresh embryo transfer

frozen-thawed embryo transfer group

EXPERIMENTAL

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.

Other: frozen-thawed embryo transfer

Interventions

fresh embryo transfer OTHER

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.

fresh embryo transfer group

frozen-thawed embryo transfer OTHER

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.

frozen-thawed embryo transfer group

Eligibility Criteria

• Age: 20 Years - 34 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• Ovulation dysfunction and failed to become pregnant from ovulation induction treatment;
• Tubal factors: unilateral or bilateral tubal obstruction, adhesion, unilateral or bilateral Salpingectomy or tubal ligation;
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (14)

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, 230022, China

Location

The First Affiliated Hospital of Lanzhou University

Lanzhou, Gansu, 730000, China

Location

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Guangzhou, Guangdong, 510120, China

Location

The sixth Affiliated Hospital of Sun Yat-Sen University

Guangzhou, Guangdong, 510655, China

Location

Guangxi Maternal and Child Health Hospital

Nanning, Guangxi, 530003, China

Location

Renmin Hospital of Wuhan University

Wuhan, Hubei, 430060, China

Location

Jiangsu Province Hospital

Nanjing, Jiangsu, 210029, China

Location

Jiangxi Maternal and Child Health Hospital

Nanchang, Jiangxi, 330006, China

Location

Reproductive Medicine Center in Shenyang City

Shenyang, Liaoning, 110000, China

Location

Reproductive medical hospital affiliated to Shandong University

Jinan, Shandong, 250001, China

Location

Yuhuangding Hospital in Yantai

Yantai, Shandong, 264000, China

Location

Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, 200127, China

Location

Shanxi Provincial Maternity and Children's Hospital

Xi’an, Shanxi, 710003, China

Location

Sir Run Run Shaw Hospital

Hangzhou, Zhejiang, 310016, China

Location

Related Publications (8)

• [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.

  BACKGROUND

• Zaat T, Zagers M, Mol F, Goddijn M, van Wely M, Mastenbroek S. Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database Syst Rev. 2021 Feb 4;2(2):CD011184. doi: 10.1002/14651858.CD011184.pub3.

  PMID: 33539543 DERIVED

• Wei D, Yu Y, Sun M, Shi Y, Sun Y, Deng X, Li J, Wang Z, Zhao S, Zhang H, Legro RS, Chen ZJ. The Effect of Supraphysiological Estradiol on Pregnancy Outcomes Differs Between Women With PCOS and Ovulatory Women. J Clin Endocrinol Metab. 2018 Jul 1;103(7):2735-2742. doi: 10.1210/jc.2018-00613.

  PMID: 29718297 DERIVED

• Zhang B, Wei D, Legro RS, Shi Y, Li J, Zhang L, Hong Y, Sun G, Zhang T, Li W, Chen ZJ. Obstetric complications after frozen versus fresh embryo transfer in women with polycystic ovary syndrome: results from a randomized trial. Fertil Steril. 2018 Feb;109(2):324-329. doi: 10.1016/j.fertnstert.2017.10.020. Epub 2018 Jan 17.

  PMID: 29338857 DERIVED

• Wei D, Zhang B, Shi Y, Zhang L, Zhao S, Du Y, Xu L, Legro RS, Zhang H, Chen ZJ. Effect of Preconception Impaired Glucose Tolerance on Pregnancy Outcomes in Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2017 Oct 1;102(10):3822-3829. doi: 10.1210/jc.2017-01294.

  PMID: 28938429 DERIVED

• Wei D, Shi Y, Li J, Wang Z, Zhang L, Sun Y, Zhou H, Xu Y, Wu C, Liu L, Wu Q, Zhuang L, Du Y, Li W, Zhang H, Legro RS, Chen ZJ. Effect of pretreatment with oral contraceptives and progestins on IVF outcomes in women with polycystic ovary syndrome. Hum Reprod. 2017 Feb;32(2):354-361. doi: 10.1093/humrep/dew325. Epub 2016 Dec 19.

  PMID: 27999118 DERIVED

• Chen ZJ, Shi Y, Sun Y, Zhang B, Liang X, Cao Y, Yang J, Liu J, Wei D, Weng N, Tian L, Hao C, Yang D, Zhou F, Shi J, Xu Y, Li J, Yan J, Qin Y, Zhao H, Zhang H, Legro RS. Fresh versus Frozen Embryos for Infertility in the Polycystic Ovary Syndrome. N Engl J Med. 2016 Aug 11;375(6):523-33. doi: 10.1056/NEJMoa1513873.

  PMID: 27509101 DERIVED

• 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.

  PMID: 24885793 DERIVED

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Infertility

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Study Officials

• Zi-jiang Chen, MD

  Repreductive medical hospital affiliated to Shandong University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Reproductive medical center of Shandong University

Study Record Dates

• First Submitted: April 18, 2013
• First Posted: April 26, 2013
• Study Start: June 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: April 16, 2014

Record last verified: 2014-04

Locations

CN (14)