Fresh Embryo Transfer, In Vitro Maturation of Oocytes, Polycystic Ovary Syndrome (PCOS)
Conditions
Keywords
in vitro maturation, The SAIGON protocol, fresh embryo transfer, GnRH-Antagonist, frozen embryo transfer
Brief summary
Assisted Reproductive Technologies (ART) aim to increase success rates while minimizing patient risks. For women with high AFC or PCOS, conventional IVF carries a high risk of OHSS (Ho et al., 2019). A modern IVF strategy to prevent this uses a GnRH agonist trigger, requiring a freeze-all and subsequent FET (Wong et al., 2017). This reduces OHSS risk but can increase time to pregnancy (Vuong et al., 2021) and treatment burden. IVM is a patient-friendly alternative that eliminates OHSS risk by avoiding high-dose gonadotropins. A 2020 trial by Vuong et al. compared CAPA-IVM-FET to conventional IVF-FET in women with high AFC. IVM yielded a comparable live birth rate (35.2%) versus IVF (43.2%), with a 0% OHSS rate in IVM compared to 0.7% in IVF (Vuong et al., 2020). The optimal transfer method (fresh or frozen) in IVM cycles is debated. A 2021 pilot RCT by Vuong et al. found a freeze-only strategy after CAPA-IVM led to a significantly higher live birth rate (60%) than a fresh transfer (20%) (Vuong et al., 2021), but increased time to pregnancy (194 vs. 150 days) (Vuong et al., 2021). A refined CAPA-IVM protocol, which uses no gonadotropins, allowed for fresh embryo transfer in the same cycle, resulting in a numerically higher ongoing pregnancy rate (43.3% vs. 33.3%) than FET (Vuong et al., 2025). This raises an important question: how does a simplified IVM strategy with fresh transfer compare to the established safety-net IVF strategy with FET? These two approaches represent opposing clinical philosophies. No large-scale study has yet compared them in women with PCOS. Therefore, this study is designed to compare the SAIGON protocol (gonadotropin-free CAPA-IVM with fresh ET) against a standard GnRH-antagonist IVF protocol with agonist trigger and subsequent FET.
Detailed description
1. Screening for eligibility and randomization: Women who are potentially eligible are provided with information about the trial. Screening is done on the day of the first visit, and patients are given informed consent form to sign before enrollment. Participants are then randomly assigned (1:1) to either the CAPA-IVM or IVF-FET group. 2. After randomisation 2.1. IVM-FRESH (The SAIGON Protocol): * Treatment begins on day 2-4 of the menstrual cycle. * Endometrial preparation uses oral estradiol valerate (Progynova®; Delpharm Lille SAS, France) 8mg/day for at least 10 days. * Immature oocyte retrieval is performed when the endometrial thickness is ≥ 8 mm. * Mature oocytes are fertilized via ICSI. * Luteal phase support is provided with vaginal progesterone (800 mg/day) + dydrogesterone (20mg/day) starting on the day of ICSI. * A fresh embryo transfer is performed three or five days after progesterone administration, depending on the embryo stage. 2.2. IVF-FET (Frozen Transfer Protocol): * This protocol uses a random start approach, beginning on the day of the patient's first visit. * Ovarian stimulation is done using a GnRH antagonist protocol with a starting dose of 150 IU/day of rFSH. * A GnRH agonist trigger is administered when at least two leading follicles reach ≥ 17 mm in diameter. * Insemination is performed using ICSI for matured oocytes. * The endometrium is prepared for frozen embryo transfer using oral oestradiol valerate (8mg/day) and vaginal progesterone (800 mg/day) + dydrogesterone (20mg/day) when endometrial thickness is ≥ 8 mm. * Surviving embryos are thawed and transferred two hours after thawing under ultrasound guidance. 3. Pregnancy and outcomes: * A pregnancy test is performed 10-14 days after embryo transfer. A positive result is a serum hCG level of ≥ 25 mIU/mL. * Both groups continue hormone supplementation if the pregnancy test is positive. * The primary outcome of the study is the live birth rate after one embryo transfer. Secondary outcomes include cumulative ongoing pregnancy, time to ongoing pregnancy, clinical pregnancy rate, miscarriage, and other treatment and pregnancy complications. * Obstetric and neonatal outcomes: All data relating to the delivery process and neonatal care will be recorded by the data management system of IVFMD.
Interventions
PROCEDUREIVM-Fresh (No gonadotropin + Fresh embryo transfer)
Patients randomized to this arm will receive estradiol valerate 8 mg/day. IVM will be performed after ≥10 days of estrogen and ET ≥8 mm. From the day of ICSI, they will continue estradiol and start vaginal progesterone 800 mg/day + dydrogesterone (20mg/day). A fresh embryo transfer will subsequently be performed.
PROCEDUREIVF-FET (GnRH-Antagonist - Agonist Trigger - Frozen embryo transfer)
Patients randomized into this group will receive FSH at a dose of 150 IU/day. Oocyte retrieval will be performed once the criteria for triggering are fulfilled, followed by embryo cryopreservation and frozen embryo transfer in the subsequent cycle. Endometrial preparation for frozen embryo transfer will be conducted using an exogenous steroids regimen. Patients will receive estradiol 8 mg/day starting from cycle days 2-3 for 10 days. When the endometrial thickness reaches ≥8 mm, luteal phase support will be initiated with vaginal progesterone 800 mg/day plus dydrogesterone 20 mg/day.
Sponsors
Mỹ Đức Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Parallel Assignment
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 42 Years
Healthy volunteers
No
Inclusion criteria
* Women aged 18 - 42 years old. * Diagnosed with PCOS, followed Rotterdam 2003 criteria (Group TREP consensus workshop, 2004) * Had fewer than three previous failed frozen embryo transfer (FET) cycles * Transferred no more than two cleavage embryos or one good-quality blastocyst or no more than two poor-quality blastocysts. * Agreeing to participate in the study
Exclusion criteria
* Having allergy and contraindications for exogenous hormone administration (e.g., breast cancer, thromboembolic disease) * Cycles with preimplantation genetic testing indication * Oocyte donation cycles * Having untreated uterine or adnexal abnormalities (e.g., intrauterine adhesions, unicornuate/ bicornuate/ arcuate uterus, large leiomyoma ≥5 cm in diameter; adenomyosis, endometrial polyp, hydrosalpinx).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Live birth rates after the one embryo transfer | At 24 weeks of gestation | Live birth was defined as the complete expulsion or extraction from a woman of a product of fertilization, after 22 completed weeks of gestational age; which, after such separation, breathes or shows any other evidence of life, such as heartbeat, umbilical cord pulsation, or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is attached. A birth weight of 500 grams or more can be used if gestational age is unknown. Live births refer to the individual newborn; for example, a twin delivery represents two live births. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative ongoing pregnancy | After 12 months of follow-up after randomisation | Cumulative ongoing pregnancy defined as the occurrence of at least one ongoing pregnancy within 12 months of follow-up after randomisation. An ongoing pregnancy is counted as 1 for each participant who achieves at least one such pregnancy within this time frame, regardless of the number of embryo transfers or pregnancies achieved. Participants who do not return for embryo transfer within the 12-month period are considered censored |
| Time to ongoing pregnancy | Up to 10 weeks after embryo placement | Time to ongoing pregnancy defined as the interval between randomization and the achievement of an ongoing pregnancy. |
| Positive pregnancy test rate | 10-14 days after embryo transfer | Positive pregnancy test rate defined as serum human chorionic gonadotropin level ≥ 25 mIU/mL. |
| Clinical pregnancy rate | 6 weeks after embryo transfer | A pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. In addition to intra-uterine pregnancy, it includes a clinically documented ectopic pregnancy. |
| Ongoing pregnancy rate | 12 weeks after embryo transfer | A pregnancy diagnosed by ultrasonographic or clinical documentation of at least one fetus with a discernible heartbeat at 12 weeks gestation or beyond |
| Implantation rate | 3 weeks after embryo transfer | The number of gestational sacs observed divided by the number of embryos transferred (usually expressed as a percentage) |
| Ectopic pregnancy rate | 2 - 4 weeks after embryo transfer | A pregnancy outside the uterine cavity, diagnosed by ultrasound, surgical visualization, or histopathology. |
| Miscarriage rate | 2-22 weeks after embryo transfer | Spontaneous loss of a clinical pregnancy before 22 completed weeks of gestational age, in which the embryo(s) or fetus(es) is/are nonviable and is/are not spontaneously absorbed or expelled from the uterus. |
| Multiple gestations rate | 5 weeks after embryo transfer | A pregnancy with more than one embryo or fetus |
| Multiple birth rate | At 22 weeks' gestation | The complete expulsion or extraction from a woman of more than one fetus, after 22 completed weeks of gestational age, irrespective of whether it is a live birth or stillbirth. Births refer to the individual newborn; for example, a twin delivery represents two births. |
| Very high birth weight | At delivery | Birth weight over 4.500 g. |
| Mode of delivery | At delivery | Vaginal delivery, Assisted vaginal delivery, C-section |
| Birth weight | At delivery | Weight of the newborn measured right after delivery |
| High birth weight | At delivery | Implies growth beyond an absolute birth weight of 4.000 g, regardless of the gestational age |
| Ovarian hyperstimulation syndrome | Up to 1 week after the oocyte retrieval in the IVF arm | Ovarian hyperstimulation syndrome (OHSS) is a potentially lethal iatrogenic complication of the early luteal phase or/and early pregnancy after ovulation induction or ovarian stimulation. OHSS was evaluated if symptoms were reported by the patient. |
| IVM oocyte retrieval cancellation | After 21 day of endometrial preparation | Record the reason for canceling in IVM arm |
| Embryo transfer cancellation | After 21 days of endometrial preparation | Record the reason for canceling. |
| Preterm birth | At delivery | Defined as delivery at \<28, \<32, \<37 completed weeks. A birth that takes place after 22 weeks and before 37 completed weeks of gestational age. |
| Gestational diabetes mellitus | At 24-28 weeks of gestation | A 75-g OGTT, with plasma glucose measurement when the patient is fasting and at 1 and 2 h, at 24-28 weeks of gestation in women not previously diagnosed with diabetes. |
| Hypertensive disorders of pregnancy | After 20 weeks of gestation | Pregnancy-induced hypertension, pre-eclampsia (early and late), eclampsia, and HELLP syndrome |
| Stillbirth | At delivery after 28 weeks of gestation | The death of a fetus before the complete expulsion or extraction from its mother after 28 completed weeks of gestational age. The death is determined by the fact that, after such separation, the fetus does not breathe or show any other evidence of life, such as heartbeat, umbilical cord pulsation, or definite movement of voluntary muscles. It includes deaths occurring during labor. |
| Very low birth weight | At delivery | Birth weight less than 1.500 g. |
| Low birth weight | At delivery | Birth weight less than 2.500 g |
| Major congenital abnormalities | During pregnancy and 12 months after delivery | Structural, functional, and genetic anomalies that occur during pregnancy, and are identified antenatally, at birth, or later in life, and require surgical repair of a defect, or are visually evident, or life-threatening, or cause death. Any congenital anomaly will be included as follows definition of congenital abnormalities in Surveillance of Congenital Anomalies by Division of Birth Defects and Developmental Disabilities, NCBDDD, Centers for Disease Control and Prevention (2020). |
| Postpartum hemorrhage | Up to one month after the delivery | Defined as a blood loss of ≥ 1000 mL, or blood loss accompanied by signs or symptoms of hypovolemia, within 24 hours after birth (including intrapartum blood loss), regardless of the mode of delivery. |
| NICU admission | Up to one month after the delivery | The admission of the newborn to the NICU |
| Neonatal mortality | Up to one month after the delivery | Death of a live-born baby within 28 days of birth. This can be divided into early neonatal mortality, if death occurs in the first seven days after birth, and late neonatal if death occurs between 8 and 28 days after delivery. |
| Gestational age at birth | At delivery | Calculated by gestational age of all live births |
Countries
Vietnam
Contacts
Primary ContactVu NA Ho, MD, PhD
Outcome results
None listed