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NCT Number: NCT06744881

CAPA - IVM in Ovulatory Infertile Women

In vitro maturation (IVM) is an assisted reproductive technology (ART) using minimal or no ovarian stimulation. In IVM, immature oocytes at the germinal vesical (GV) or metaphase I (MI) stage retrieved from small antral follicles are cultured to reach metaphase II (MII) (ASRM, 2021).

Since the first successful IVM baby was reported, subsequent studies have been mostly focused on patients with polycystic ovary syndrome (PCOS) to reduce the risks associated with ovarian stimulation such as ovarian hyperstimulation syndrome (OHSS), thromboembolic complications and ovarian torsion (Cha et al., 1991; Chian et al., 2000). Numerous IVM protocols have been applied with or without FSH or hCG priming and using one step or two steps culture system to gain the optimum oocyte maturation rate, blastulation rate and live birth rate (Sanchez et al., 2019; De Vos et al., 2021).

A randomized controlled trial (RCT) conducted on women with high antral follicle count, including women with PCOS, indicated that CAPA-IVM was non-inferior to conventional IVF (Vuong et al., 2020). Studies also showed that the mental and motor development of children born after IVM was similar to that of those born after IVF and naturally conceived (Nguyen et al., 2022; Vuong et al., 2022). Additionally, IVM is considered an effective treatment for women with gonadotropin resistant ovary syndrome to have children with their own oocytes (Le et al., 2021). IVM is also a viable option for fertility preservation for women with cancer in need of urgent treatment and contraindicated to hormonal stimulation (Grynberg et al., 2022).

There is little evidence on the effectiveness of IVM on women without PCOS. Junk et al have compared the effectiveness of IVM between women with polycystic ovaries (PCO) and polycystic ovary syndrome (Junk and Yeap, 2012). Women with PCO had significantly lower oocytes collected than those with PCOS (p<0,001), maturation rate, blastocyst development rate, and clinical pregnancy rate were comparable between two groups (Junk and Yeap, 2012). Another study indicated the maturation rate after standard IVM of ovarian tissue-derived oocytes collected from cancer patients was 8-67% (Segers et al., 2020). A study conducted by Kirillova on ovarian cancer patients with normal to high ovarian reserve showed that CAPA-IVM resulted in a higher maturation rate in ovarian tissue oocytes compared to standard IVM (56% vs 36%, p=0.0045) (Kirillova et al., 2021).

Recently, IVF/ICSI has been indicated in almost all infertility patients without PCOS. A randomized controlled trial on non-PCOS women with high antral follicle counts revealed no significant differences between IVM and conventional IVF regarding the ongoing pregnancy rate, live birth rate and the incidence of pregnancy and perinatal complications (Vuong et al., 2020). IVM offers numerous advantages due to the concept of using mild or no stimulation. The risk of ovarian hyperstimulation syndrome is largely eliminated, the cost of treatment is notably reduced. IVM is also more convenient as it requires fewer patient visits, ultrasounds and blood tests (Ho and Vuong, 2023).

Therefore, this pilot study is to evaluate the effectiveness and safety of CAPA-IVM in ovulatory infertile women and evaluate its success rate in relation to their ovarian reserve.

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Key information

Age range

18 year–37 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

About this study

  • Screening for eligibility and randomization
  • This trial will be conducted at My Duc Hospital, Ho Chi Minh City, Viet Nam.
  • Eligibility screening will be performed on the first visit.
  • Patients meeting the inclusion criteria will be invited to participate in the study. Patients will be provided with study information and consent forms. The investigator will collect signed consent forms from all participants.
  • Oocyte retrieval:

On days 2-4 of the menstrual cycle, after patients have consented to CAPA-IVM, they will undergo oocyte aspiration anytime thereafter but no later than day 6 of the cycle.

Cycle programming with oral contraceptives or progestogens, nor ovarian stimulation with rFSH or hMG preparations nor the use GnRH analogues are allowed. The use of oral contraceptives will be considered from the second cohort of patients onwards in case the timing/scheduling of the oocyte retrieval needs to be optimized. No hCG or GnRH agonist preparations will be administered for triggering ovarian maturation prior to oocyte retrieval.

  • Capacitation in vitro maturation The follicular aspirates are collected and filtered through a cell strainer. After collection, COCs are washed and transferred to a four-well dish, containing CAPA medium. Following 24 hours of incubation in CAPA media, COCs complexes are cultured in IVM medium for 30 hours. Following IVM culture, oocytes are mechanically and enzymatically denuded from their cumulus layers under a stereomicroscope and oocyte maturation is assessed under the inverted microscope
  • Fertilization:

ICSI will be used to fertilize mature oocytes. Embryos will be cryopreserved at the cleavage-stage embryo (day 3) if the patient has less than 4 embryos. Patients with 4 or more embryos will be counseled on blastocyst culture (day 5) according to the IVFMD protocol. All viable embryos will be cryopreserved.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Ageing from 18 to 37.
  • Women without PCOS:
  • Having regular periods: >24 days and <35 days.
  • And not having clinical hyperandrogenism or biochemical hyperandrogenism.
  • And not presenting with peripheral distribution of polycystic ovaries on ultrasound.
  • Antral follicle count 15 ≤AFC ≤ 24 and Anti-Mullerian Hormone 2,1 ≤ AMH ≤ 5 ng/mL)
  • Having indication for ART
  • First ART cycle.
  • No ovarian stimulation 3 months prior to study entry
  • Agree to have all embryos frozen on day 3 or day 5.
  • Agree to transfer no more than 02 cleavage-stage embryos or 01 blastocyst-stage embryo in a subsequent embryo transfer.
  • Agree to participate in the study (Agree to undergo CAPA-IVM).

Exclusion criteria

  • Donor oocyte cycles.
  • Uterine abnormalities (adenomyosis, leiomyoma (≥5 cm), bicornuate uterus, intrauterine adhesion).
  • Prior ovarian surgery.
  • Surgically extracted sperm (by PESA, TESE or micro TESE).

Treatment and study plan

CAPA-IVM

Procedure

On days 2-4 of the menstrual cycle, after patients have consented to CAPA-IVM, they will undergo oocyte aspiration anytime thereafter but no later than day 6 of the cycle. Pre-maturation will last for 24-30 hours. ICSI will be used for insemination. Freeze-only on day 3 or day 5 and frozen embryo transfer will be performed on the subsequent cycle using HRT protocol with a maximum of 2 embryos transfer

Primary outcomes

  1. Number of metaphase II oocytes available after CAPA-IVM culture

    Time frame: 24-48 hours after eggs retrieved

    This will be analyzed according to the patient's ovarian reserve

Secondary outcomes

  1. Number of patients aspirated without oocytes

    Time frame: OR day

    Count the number of patients aspirated without oocytes

  2. Number of patients without mature oocytes after CAPA-IVM

    Time frame: OR day

    Count the number of patients without mature oocytes

  3. Number of patients without embryos

    Time frame: OR day

    Count the number of patients without embryos

  4. Oocyte maturation rate

    Time frame: 24-48 hours after eggs retrieval.

    The oocyte maturation rate is calculated by dividing the number of MII oocytes after CAPA-IVM by the number of cumulus-oocyte complex (COC) retrieved

  5. Fertilization rate

    Time frame: ICSI day

    Number of fertilized oocytes divided by the number of ICSI oocytes

  6. Number of fertilized oocytes

    Time frame: 16-18 hours after ICSI

    Count the number of 2PN oocytes at 16-18 hours after ICSI

  7. Number of day-3 embryos

    Time frame: 64±2 hours after ICSI

    Count the number of day-3 embryos at 64±2 hours after ICSI

  8. Day-3 embryo rate

    Time frame: 64±2 hours after ICSI

    Number of day-3 embryos divided by the number of fertilized oocytes

  9. Number of good quality day-3 embryos

    Time frame: 64±2 hours after ICSI

    Count the number of day-3 embryos graded as grade 1 and grade 2.

  10. Number of day-3 embryos frozen

    Time frame: 64±2 hours after ICSI

    Count the number of day-3 embryos frozen

  11. Number of day-5/6 embryos

    Time frame: 114±2/140±2 after ICSI

    Count the number of day-5 embryos at 114±2/140±2 after ICSI

  12. Day-5/6 embryo rate

    Time frame: 114±2/140±2 after ICSI

    Number of day-5/6 embryos divided by the number of fertilized oocytes

  13. Number of good quality day-5/6 embryos

    Time frame: 114±2/140±2 after ICSI

    Count the number of day-5/6 embryos graded as grade 1 and grade 2

  14. Number of day-5/6 embryos frozen

    Time frame: 114±2/140±2 after ICSI

    Count the number of day-5/6 embryos frozen

Study contacts

Contact information is provided by the study sponsor or research team.

Ho Long Le, MD

CONTACT

[email protected]

+84 356177147

Sponsors and collaborators

Lead sponsor

Mỹ Đức Hospital

Other

Registry information

Official study title

The Effectiveness and Safety of CAPA - IVM in Ovulatory Infertile Women: a Pilot Study

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
Dec 20, 2024
Registry last updated
Dec 27, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.