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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
600
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.
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.
IVFMD - My Duc Hospital
Ho Chi Minh City, Vietnam
RECRUITINGLive birth rates after the one embryo transfer
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.
Time frame: At 24 weeks of gestation
Cumulative ongoing pregnancy
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 frame: After 12 months of follow-up after randomisation
Time to ongoing pregnancy
Time to ongoing pregnancy defined as the interval between randomization and the achievement of an ongoing pregnancy.
Time frame: Up to 10 weeks after embryo placement
Positive pregnancy test rate
Positive pregnancy test rate defined as serum human chorionic gonadotropin level ≥ 25 mIU/mL.
Time frame: 10-14 days after embryo transfer
Clinical pregnancy rate
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.
Time frame: 6 weeks after embryo transfer
Ongoing pregnancy rate
A pregnancy diagnosed by ultrasonographic or clinical documentation of at least one fetus with a discernible heartbeat at 12 weeks gestation or beyond
Time frame: 12 weeks after embryo transfer
Implantation rate
The number of gestational sacs observed divided by the number of embryos transferred (usually expressed as a percentage)
Time frame: 3 weeks after embryo transfer
Ectopic pregnancy rate
A pregnancy outside the uterine cavity, diagnosed by ultrasound, surgical visualization, or histopathology.
Time frame: 2 - 4 weeks after embryo transfer
Miscarriage rate
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.
Time frame: 2-22 weeks after embryo transfer
Multiple gestations rate
A pregnancy with more than one embryo or fetus
Time frame: 5 weeks after embryo transfer
Multiple birth rate
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.
Time frame: At 22 weeks' gestation
Mode of delivery
Vaginal delivery, Assisted vaginal delivery, C-section
Time frame: At delivery
Birth weight
Weight of the newborn measured right after delivery
Time frame: At delivery
Gestational age at birth
Calculated by gestational age of all live births
Time frame: At delivery
Ovarian hyperstimulation syndrome
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.
Time frame: Up to 1 week after the oocyte retrieval in the IVF arm
IVM oocyte retrieval cancellation
Record the reason for canceling in IVM arm
Time frame: After 21 day of endometrial preparation
Embryo transfer cancellation
Record the reason for canceling.
Time frame: After 21 days of endometrial preparation
Preterm birth
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.
Time frame: At delivery
Gestational diabetes mellitus
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.
Time frame: At 24-28 weeks of gestation
Hypertensive disorders of pregnancy
Pregnancy-induced hypertension, pre-eclampsia (early and late), eclampsia, and HELLP syndrome
Time frame: After 20 weeks of gestation
Stillbirth
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.
Time frame: At delivery after 28 weeks of gestation
Very low birth weight
Birth weight less than 1.500 g.
Time frame: At delivery
Low birth weight
Birth weight less than 2.500 g
Time frame: At delivery
High birth weight
Implies growth beyond an absolute birth weight of 4.000 g, regardless of the gestational age
Time frame: At delivery
Very high birth weight
Birth weight over 4.500 g.
Time frame: At delivery
Major congenital abnormalities
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).
Time frame: During pregnancy and 12 months after delivery
Postpartum hemorrhage
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.
Time frame: Up to one month after the delivery
NICU admission
The admission of the newborn to the NICU
Time frame: Up to one month after the delivery
Neonatal mortality
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.
Time frame: Up to one month after the delivery
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