A recent study published in Cureus has found that two common ovarian stimulation methods used in IVF—progesterone-primed ovarian stimulation (PPOS) and gonadotropin-releasing hormone (GnRH) antagonist protocols—deliver similar outcomes for patients. The research focused on how these methods affect ovarian response and pregnancy rates during IVF treatment.
Background: What Are COS Protocols?
Controlled ovarian stimulation (COS) protocols help regulate hormone levels in women undergoing IVF. Traditionally, GnRH agonists and antagonists are used to suppress natural production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). More recently, PPOS protocols have gained popularity, especially in Japan, where they reduce the need for frequent hospital visits.
However, PPOS comes with a drawback—it causes early changes in the uterine lining, making fresh embryo transfer impossible. Because of this, PPOS requires a “freeze-all” approach, where embryos are frozen for later transfer.
Study Design and Participants
The study was retrospective and observational. It compared the outcomes of PPOS and GnRH antagonist cycles using a fertility drug called follitropin delta. Participants were Japanese women aged 20 to 45 with healthy ovarian function and anti-Müllerian hormone levels of at least 0.8 ng/mL.
Additional requirements included:
−A body mass index (BMI) between 18 and 30
−Up to three prior IVF egg retrievals
−Use of skilled physicians for egg retrieval
−All embryos frozen for later use
Stimulation began on the second or third day of each woman’s menstrual cycle.
Treatment Methods
Women in the GnRH antagonist group received cetrorelix injections to block LH starting on day 5 or 6 of the cycle. Women in the PPOS group took 10 mg of dydrogesterone by mouth twice a day from the beginning of stimulation until egg retrieval.
All participants had blood tests and ultrasound checks on stimulation days 6, 8 to 10, and on the trigger day.
Egg Retrieval and Fertilization Process
Eggs were collected about 36 hours after giving a GnRH agonist to trigger final egg maturation. Fertilization was done using either standard IVF or intracytoplasmic sperm injection (ICSI) on the same day.
The thickness of the uterine lining was measured around day 14 of the cycle. If it was at least 8 mm, the patient received vaginal progesterone to prepare for embryo transfer.
The main focus of the study was clinical pregnancy rates. Researchers also looked at how many eggs were retrieved and how many blastocysts (advanced embryos) were formed. The analysis included data from 149 GnRH antagonist cycles and 147 PPOS cycles. They also reviewed the results based on different age groups.
Key Results: Egg and Embryo Outcomes
The number of eggs retrieved was similar between the two groups:
GnRH antagonist: 8.9 ± 6.4 eggs
PPOS: 9.4 ± 5.6 eggs
The number of blastocysts formed showed a slight increase in the PPOS group:
GnRH antagonist: 3.4 ± 3.2
PPOS: 4.1 ± 3.2
The only major difference in baseline characteristics was that the PPOS group had slightly higher FSH levels.
Results by Age Group
When results were broken down by age, here’s what the data showed:
Under 35 years:
−Eggs: 10.9 (GnRH) vs 11.7 (PPOS)
−Blastocysts: 4.7 (GnRH) vs 5.4 (PPOS)
Age 35–39:
−Eggs: 8.7 (GnRH) vs 9.1 (PPOS)
−Blastocysts: 3.2 (GnRH) vs 4.2 (PPOS)
Age 40 and over:
−Eggs: 6.4 (GnRH) vs 7.6 (PPOS)
−Blastocysts: 2.2 (GnRH) vs 2.7 (PPOS)
While the number of eggs did not vary significantly, PPOS showed a trend of producing more blastocysts, particularly among women aged 35–39.
Pregnancy Outcomes
The study found no meaningful difference in pregnancy success between the two protocols.
Clinical pregnancy rates:
66.7% (GnRH) vs 63.2% (PPOS)
Ongoing pregnancy rates:
66.7% (GnRH) vs 55.2% (PPOS)
According to the researchers, both protocols are similarly effective. However, PPOS may offer slight advantages in embryo development across all age groups.
Conclusion
The study, which analyzed two years of IVF data from a single clinic, supports the idea that PPOS and GnRH antagonist protocols are both valid options for ovarian stimulation. While pregnancy rates were nearly identical, PPOS showed a tendency to yield more developed embryos, especially in older women.
This information may help fertility specialists personalize treatment plans based on each patient’s needs, lifestyle, and medical history.
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