IVM Versus Standard IVF in Infertile Patients Diagnosed With PCOS

In Vitro Maturation Versus Standard in Vitro Fertilization in Infertile Patients Diagnosed With Polycystic Ovaries Syndrome: a Study Protocol for a Single-center Prospective, Randomized Controlled Clinical Trial

A single center, prospective, open-label, non-inferiority randomized controlled clinical trials (1:1 treatment ratio) regarding pregnancy outcomes between IVM and standard IVF among infertility couples with PCOS in China.

Study Overview

• Status: Unknown
• Conditions: PCOS
• Intervention / Treatment: Procedure: standard IVF; Drug: In vitro maturation

Detailed Description

A single center, randomized controlled clinical trial will enroll 350 couples with PCOS undergoing their first cycle of IVF. The participation in this study will be approximately 2 years with a total of 7 visits from the cycle beginning, pregnancy to delivery. On day 2 or day 3 following the onset of menstrual bleeding, eligible patients will be allocated to two groups at a ratio of 1:1- IVM protocol, and standard IVF protocol. All participants will be randomized through stratified block randomization according to the study sites.

• Study Type: Interventional
• Enrollment (Actual): 350
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100191
      • Peking University Third Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Infertile couples scheduled for their first IVF cycle.
2. Women diagonosed with polycystic ovarian syndrome.
3. Voluntary participation and informed consent obtained.

Exclusion Criteria:

1. Couple with contraindication for IVF or ICSI.
2. Couples receiving donor sperm or donor eggs.
3. Couples with indications or have plan to receive PGD and PGS.
4. Sperm analysis diagnosed as azoospermia;
5. Either male partner or female partner with an abnormal chromosome karyotype (chromosome polymorphisms was not included).
6. Women who have undergone unilateral ovariectomy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: standard IVF; On the Day2/3 of the menstrual cycle, qualified participants will be randomized into either of two groups. Participants in group A will receive standard IVF procedure. Other standard assisted reproductive treatments are similar and parallel between two groups.	Procedure: standard IVF; Ovarian stimulation will be performed by a standard protocol using gonadotrophin-releasing hormone antagonist (GnRH-ant) in association with recombinant FSH (rFSH) and human chorionic gonadotrophin (hCG).Oocyte retrieval is scheduled for 36 (±2) after hCG injection.The retrieved cumulus oocyte complexes (COC) will be inseminated using ICSI or conventional IVF according to the seman analysis. All embryos will be cultured to blastocyst stage and be vitrified.
Active Comparator: In vitro maturation; On the Day2/3 of the menstrual cycle, qualified participants will be randomized into either of two groups. Participants in group B will receive IVM procedure.Other standard assisted reproductive treatments are similar and parallel between two groups.	Drug: In vitro maturation; Controlled ovarian stimulation protocol will not performed in this group patients. Transvaginal ultrasound scanning was examined on natural cycle to monitor the follicle size in group B participants. Oocyte retrieval was scheduled once the endometrium had reached at least 6 mm in thickness and there was no follicle larger than 10 mm. After oocyte retrieval, the COCs will be cultured for 28-32h in special IVM media in order to get the matured oocytes. All the metaphase II (MII) oocytes were inseminated by means of intracytoplasmic sperm injection (ICSI). All embryos will be cultured to blastocyst stage and be vitrified.; Other Names: IVM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the proportion of ongoing pregnancy leading to live birth	number of ongoing pregnancy leading to live birth resulting from the first oocyte retrieval cycle after the randomization ( 6 month) divided by the number of patients with oocyte retrieval	after 22 weeks of gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
implantation	Number of gestational sacs observed per embryo transferred	28 days after embryo transfer
clinical pregnancy	one or more observed gestational sac or definitive clinical signs of pregnancy under ultrasonography at 7 weeks after embryo transfer (including clinical documented ectopic pregnancy)	7 weeks after embryo transfer
Miscarriage	Spontaneous loss of an intra-uterine pregnancy prior to 28 completed weeks of gestational age	28 weeks of gestation
Preterm birth	Birth of a fetus delieved after 28 and before 37 completed weeks of gestational age in participants confirmed ongoing pregnancy	28-37 weeks of pregnancy
Birth weight	Including low birth weight (defined as weight <2500 gm at birth), very low birth weight (defined as < 1500 gm at birth), high birth weight (defined as > 4000 gm at birth) and very high birth weight (defined as > 4500 gm at birth).	within 2 weeks after live birth
Large for gestational age	Birth weight >90th centile for gestation, based on standardised ethnicity based charts.	within 2 weeks after live birth
Small for gestational age	Less than 10th centile for gestational age at delivery based on standardised ethnicity based charts.	within 2 weeks after live birth
Congenital anomaly	Any congenital anomaly will be included diagnosed by physical examinition, ultrasound or necessary testing (including CT, X-ray etc.)	within 2 weeks after live birth
Perinatal mortality	Fetal or neonatal death occurring during late pregnancy (at 28 completed weeks of gestational age and later), during childbirth, or up to seven completed days after birth.	within 2 weeks after live birth
Moderate/severe ovarian hyperstimulation syndrome (OHSS)	exaggerated systemic response to ovarian stimulation characterized by a wide spectrum of clinical and laboratory manifestations. It is classified as mild, moderate, or severe according to the degree of abdominal distention, ovarian enlargement and respiratory hemodynamic, and metabolic complications. Diagosised by ultrasound, blood testing and physical examination according the Chinese Medical Guildline.	From date of controlled ovarian hyperstimulation until the date of oocyte retrieval, assesses about 14-16 days.

Collaborators and Investigators

• Sponsor: Jie Qiao
• Investigators: Study Director: Jie Qiao, Peking University Third Hospital

Publications and helpful links

General Publications

• Zheng X, Guo W, Zeng L, Zheng D, Yang S, Xu Y, Wang L, Wang R, Mol BW, Li R, Qiao J. In vitro maturation without gonadotropins versus in vitro fertilization with hyperstimulation in women with polycystic ovary syndrome: a non-inferiority randomized controlled trial. Hum Reprod. 2022 Jan 28;37(2):242-253. doi: 10.1093/humrep/deab243.
• Zheng X, Guo W, Zeng L, Zheng D, Yang S, Wang L, Wang R, Mol BW, Li R, Qiao J. Live birth after in vitro maturation versus standard in vitro fertilisation for women with polycystic ovary syndrome: protocol for a non-inferiority randomised clinical trial. BMJ Open. 2020 Apr 14;10(4):e035334. doi: 10.1136/bmjopen-2019-035334.

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2018
• Primary Completion (Anticipated): June 1, 2020
• Study Completion (Anticipated): October 1, 2020

Study Registration Dates

• First Submitted: January 29, 2018
• First Submitted That Met QC Criteria: March 6, 2018
• First Posted (Actual): March 13, 2018

Study Record Updates

• Last Update Posted (Actual): October 29, 2019
• Last Update Submitted That Met QC Criteria: October 28, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: polycystic ovarian syndrome; oocyte; in vitro maturation
• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: IVM/IVF-PCOS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No