News | Study: Short GnRH antagonist protocol may significantly reduce OHSS risk in IVF patients
As assisted reproduction advances, the short GnRH antagonist protocol may become an important strategy for reducing ovarian hyperstimulation syndrome (OHSS). Dr. Pedro Melo of the Tommy's National Centre for Miscarriage Research at the University of Birmingham presented the findings at the 38th ESHRE annual meeting.
This Cochrane review analyzed 171 randomized controlled trials involving about 37,000 women undergoing IVF or intracytoplasmic sperm injection (ICSI), assessing the efficacy and safety of 56 ovarian-stimulation protocols.
Live birth rates differed little among protocols, but treatment complications varied substantially. Most importantly, compared with the traditional long GnRH agonist protocol, the short GnRH antagonist protocol reduced OHSS risk by up to 52% in patients expected to have a normal or high ovarian response.
Evolution of IVF stimulation: from natural cycles to individualized stimulation
Since Louise Brown, the first IVF baby, was born in the United Kingdom in 1978, assisted reproduction has shifted from natural to stimulated cycles. Natural cycles made history but were inefficient and difficult to reproduce, so specialists adopted gonadotropin stimulation to retrieve more oocytes and improve pregnancy rates.
Gonadotropins initially came from natural sources such as human menopausal gonadotropin (hMG). With recombinant technology, recombinant FSH is now the most commonly used stimulation drug.
Most protocols also use pituitary suppression with a GnRH agonist or antagonist to prevent premature ovulation and allow precise scheduling of oocyte retrieval.
The traditional long GnRH agonist protocol takes several weeks to suppress the pituitary, making the cycle five to six weeks long. The newer short antagonist protocol can be completed in two to three weeks.
OHSS: one of the most serious complications of assisted reproduction
OHSS is a major concern during IVF, particularly in patients with normal or high ovarian reserve. Mild OHSS affects up to 33% of IVF patients. Severe cases are uncommon, around 1%, but may cause circulatory, respiratory, or kidney problems.
The review found that the long agonist protocol carries a clearly higher OHSS risk than the short antagonist protocol. The latter shortens treatment, requires fewer injections, has comparable efficacy, and substantially lowers OHSS risk.
The mechanism is not fully understood. Researchers suggest antagonists may avoid the ovarian “flare effect”; antagonist protocols also commonly use an hCG-free trigger, while hCG is a major contributor to OHSS.
Expert recommendation: prioritize short protocols for high responders and egg donors
“For patients predicted to have a normal or high ovarian response, a long protocol does not improve live birth rates and may increase OHSS,” Dr. Melo said. He considered continued use of long protocols in these patients, especially egg donors, “difficult to justify.”
“Antagonist protocols are shorter, require fewer injections, are no less effective, and, most importantly, significantly reduce patient risk. These findings strongly support current clinical guidelines,” he added.
Dr. Melo noted that the review did not analyze cumulative live birth rates from all fresh and frozen embryos produced in one stimulation cycle. More research is needed on this measure of IVF success.
Source:
Collected online
Published 2025-05-10
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News | Study: Short GnRH antagonist protocol may significantly reduce OHSS risk in IVF patients
News | Study: Short GnRH antagonist protocol may significantly reduce OHSS risk in IVF patients
As assisted reproduction advances, the short GnRH antagonist protocol may become an important strategy for reducing ovarian hyperstimulation syndrome (OHSS). Dr. Pedro Melo of the Tommy's National Centre for Miscarriage Research at the University of Birmingham presented the findings at the 38th ESHRE annual meeting.
This Cochrane review analyzed 171 randomized controlled trials involving about 37,000 women undergoing IVF or intracytoplasmic sperm injection (ICSI), assessing the efficacy and safety of 56 ovarian-stimulation protocols.
Live birth rates differed little among protocols, but treatment complications varied substantially. Most importantly, compared with the traditional long GnRH agonist protocol, the short GnRH antagonist protocol reduced OHSS risk by up to 52% in patients expected to have a normal or high ovarian response.
Evolution of IVF stimulation: from natural cycles to individualized stimulation
Since Louise Brown, the first IVF baby, was born in the United Kingdom in 1978, assisted reproduction has shifted from natural to stimulated cycles. Natural cycles made history but were inefficient and difficult to reproduce, so specialists adopted gonadotropin stimulation to retrieve more oocytes and improve pregnancy rates.
Gonadotropins initially came from natural sources such as human menopausal gonadotropin (hMG). With recombinant technology, recombinant FSH is now the most commonly used stimulation drug.
Most protocols also use pituitary suppression with a GnRH agonist or antagonist to prevent premature ovulation and allow precise scheduling of oocyte retrieval.
The traditional long GnRH agonist protocol takes several weeks to suppress the pituitary, making the cycle five to six weeks long. The newer short antagonist protocol can be completed in two to three weeks.
OHSS: one of the most serious complications of assisted reproduction
OHSS is a major concern during IVF, particularly in patients with normal or high ovarian reserve. Mild OHSS affects up to 33% of IVF patients. Severe cases are uncommon, around 1%, but may cause circulatory, respiratory, or kidney problems.
The review found that the long agonist protocol carries a clearly higher OHSS risk than the short antagonist protocol. The latter shortens treatment, requires fewer injections, has comparable efficacy, and substantially lowers OHSS risk.
The mechanism is not fully understood. Researchers suggest antagonists may avoid the ovarian “flare effect”; antagonist protocols also commonly use an hCG-free trigger, while hCG is a major contributor to OHSS.
Expert recommendation: prioritize short protocols for high responders and egg donors
“For patients predicted to have a normal or high ovarian response, a long protocol does not improve live birth rates and may increase OHSS,” Dr. Melo said. He considered continued use of long protocols in these patients, especially egg donors, “difficult to justify.”
“Antagonist protocols are shorter, require fewer injections, are no less effective, and, most importantly, significantly reduce patient risk. These findings strongly support current clinical guidelines,” he added.
Dr. Melo noted that the review did not analyze cumulative live birth rates from all fresh and frozen embryos produced in one stimulation cycle. More research is needed on this measure of IVF success.
Source:
Collected online