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

Primary Purpose

Polycystic Ovary Syndrome, Infertility

Status
Unknown status
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
fresh embryo transfer
frozen-thawed embryo transfer
Sponsored by
Zi-jiang Chen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Polycystic Ovary Syndrome focused on measuring Polycystic Ovary Syndrome, Infertility, In-vitro fertilization, fresh embryo transfer, frozen-thawed embryo transfer

Eligibility Criteria

20 Years - 34 Years (Adult)FemaleDoes not accept 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.

Sites / Locations

  • The First Affiliated Hospital of Anhui Medical University
  • The First Affiliated Hospital of Lanzhou University
  • Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
  • The sixth Affiliated Hospital of Sun Yat-Sen University
  • Guangxi Maternal and Child Health Hospital
  • Renmin Hospital of Wuhan University
  • Jiangsu Province Hospital
  • Jiangxi Maternal and Child Health Hospital
  • Reproductive Medicine Center in Shenyang City
  • Reproductive medical hospital affiliated to Shandong University
  • Yuhuangding Hospital in Yantai
  • Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine
  • Shanxi Provincial Maternity and Children's Hospital
  • Sir Run Run Shaw Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

fresh embryo transfer group

frozen-thawed embryo transfer group

Arm 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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Ovarian hyperstimulation syndrome (OHSS) incidence
clinical pregnancy rate
This will be based on the visualization of a intrauterine gestational sac by ultrasound.
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.
ectopic pregnancy rate
singleton live birth rate
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.
Congenital Anomalies rate
We will collect all recognized fetal and infant anomalies that occur within the trial.
neonatal complication rate
We will collect complications that occur in the neonate including admission to the neonatal intensive care unit (NICU), hospitalization, etc.

Full Information

First Posted
April 18, 2013
Last Updated
April 14, 2014
Sponsor
Zi-jiang Chen
Collaborators
The First Affiliated Hospital with Nanjing Medical University, Sixth Affiliated Hospital, Sun Yat-sen University, Anhui Medical University, RenJi Hospital, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, LanZhou University, Guangxi provincial maternal and chidren's hospital, Renmin Hospital of Wuhan University, Yantai Yuhuangding Hospital, Jiangxi Maternal and Child Health Hospital, Sir Run Run Shaw Hospital, Shanxi Provincial Maternity and Children's Hospital, Reproductive Medicine Center in Shenyang City
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1. Study Identification

Unique Protocol Identification Number
NCT01841528
Brief Title
Live Birth After Fresh Embryo Transfer Vs Frozen-thawed Embryo Transfer in Women With Polycystic Ovary Syndrome
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2014
Overall Recruitment Status
Unknown status
Study Start Date
June 2013 (undefined)
Primary Completion Date
June 2015 (Anticipated)
Study Completion Date
June 2015 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Zi-jiang Chen
Collaborators
The First Affiliated Hospital with Nanjing Medical University, Sixth Affiliated Hospital, Sun Yat-sen University, Anhui Medical University, RenJi Hospital, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, LanZhou University, Guangxi provincial maternal and chidren's hospital, Renmin Hospital of Wuhan University, Yantai Yuhuangding Hospital, Jiangxi Maternal and Child Health Hospital, Sir Run Run Shaw Hospital, Shanxi Provincial Maternity and Children's Hospital, Reproductive Medicine Center in Shenyang City

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycystic Ovary Syndrome, Infertility
Keywords
Polycystic Ovary Syndrome, Infertility, In-vitro fertilization, fresh embryo transfer, frozen-thawed embryo transfer

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
fresh embryo transfer group
Arm Type
Experimental
Arm 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.
Arm Title
frozen-thawed embryo transfer group
Arm Type
Experimental
Arm 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.
Intervention Type
Other
Intervention Name(s)
fresh embryo transfer
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
frozen-thawed embryo transfer
Intervention Description
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.
Primary Outcome Measure Information:
Title
live birth rate
Description
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.
Time Frame
10 months for group A, 12 months for group B
Secondary Outcome Measure Information:
Title
Ovarian hyperstimulation syndrome (OHSS) incidence
Time Frame
2 months in maximum estimated
Title
clinical pregnancy rate
Description
This will be based on the visualization of a intrauterine gestational sac by ultrasound.
Time Frame
35 days after embryo transfer
Title
Pregnancy Loss rate
Description
Loss of pregnancy will be defined by any positive pregnancy test that does not result in a live birth and will be tracked.
Time Frame
28 weeks gestation in maximum
Title
ectopic pregnancy rate
Time Frame
7~8 weeks gestation
Title
singleton live birth rate
Time Frame
10 months for group A, 12 months for group B
Title
pregnancy complication rate
Description
Complications of pregnancy including gestational hypertension, diabetes, preterm labor, disorders of placentation will be collected in all patients with ongoing clinical pregnancies.
Time Frame
10 months for group A, 12 months for group B
Title
Congenital Anomalies rate
Description
We will collect all recognized fetal and infant anomalies that occur within the trial.
Time Frame
10 months for group A, 12 months for group B
Title
neonatal complication rate
Description
We will collect complications that occur in the neonate including admission to the neonatal intensive care unit (NICU), hospitalization, etc.
Time Frame
within one month after labor

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
34 Years
Accepts Healthy Volunteers
No
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: 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. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zi-jiang Chen, MD
Organizational Affiliation
Repreductive medical hospital affiliated to Shandong University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Affiliated Hospital of Anhui Medical University
City
Hefei
State/Province
Anhui
ZIP/Postal Code
230022
Country
China
Facility Name
The First Affiliated Hospital of Lanzhou University
City
Lanzhou
State/Province
Gansu
ZIP/Postal Code
730000
Country
China
Facility Name
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510120
Country
China
Facility Name
The sixth Affiliated Hospital of Sun Yat-Sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510655
Country
China
Facility Name
Guangxi Maternal and Child Health Hospital
City
Nanning
State/Province
Guangxi
ZIP/Postal Code
530003
Country
China
Facility Name
Renmin Hospital of Wuhan University
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430060
Country
China
Facility Name
Jiangsu Province Hospital
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210029
Country
China
Facility Name
Jiangxi Maternal and Child Health Hospital
City
Nanchang
State/Province
Jiangxi
ZIP/Postal Code
330006
Country
China
Facility Name
Reproductive Medicine Center in Shenyang City
City
Shenyang
State/Province
Liaoning
ZIP/Postal Code
110000
Country
China
Facility Name
Reproductive medical hospital affiliated to Shandong University
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250001
Country
China
Facility Name
Yuhuangding Hospital in Yantai
City
Yantai
State/Province
Shandong
ZIP/Postal Code
264000
Country
China
Facility Name
Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200127
Country
China
Facility Name
Shanxi Provincial Maternity and Children's Hospital
City
Xi'an
State/Province
Shanxi
ZIP/Postal Code
710003
Country
China
Facility Name
Sir Run Run Shaw Hospital
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310016
Country
China

12. IPD Sharing Statement

Citations:
Citation
[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.
Results Reference
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Live Birth After Fresh Embryo Transfer Vs Frozen-thawed Embryo Transfer in Women With Polycystic Ovary Syndrome

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