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Stimulation and ovarian hyperstimulation syndrome

Not eliminated. Three things reduce it, and each has a trade-off.

Ovarian hyperstimulation syndrome is the main serious complication of the drug phase of IVF. You will often be told it is now rare. It is less common than it was, and "rare" overstates it.

In recent large randomized trials of fresh transfer, hyperstimulation ran at 2.0% in ovulatory women without polycystic ovary syndrome and 7.1% in women with PCOS. A prospective series of 1,058 retrievals recorded severe hyperstimulation in 2.7%.

Three changes reduce it, and each buys something at a price:

ChangeEffect on hyperstimulationWhat it costs
Antagonist rather than long agonist protocolRoughly 11% falls to 6% to 9%No loss of live birth. More cycles cancelled for poor response.
GnRH agonist trigger instead of hCGRoughly 5% falls to between nil and 2%In a fresh transfer, live birth roughly halves in that cycle
Freezing all embryos rather than a fresh transferRoughly 3% falls to 1%No loss of cumulative live birth, but higher blood pressure risk in pregnancy
The trade-off that is most often left outThe agonist trigger nearly abolishes hyperstimulation. In fresh cycles using your own eggs, the pooled trials found live birth fell substantially: in the reviewers' own absolute terms, for a woman with a 31% chance of live birth with HCG, the chance with a GnRH agonist would be between 12% and 24%.

That penalty does not apply if the plan is to freeze everything and transfer later, and it did not appear in donor-recipient cycles. So the agonist trigger is a good choice combined with a freeze-all plan and a poor one combined with a fresh transfer. If it is offered to you, ask which plan it is part of.

The extreme end of what protocol choice can do: in 4,052 donor cycles, every one of the 22 cases of moderate or severe hyperstimulation occurred in an hCG-triggered cycle. There were none among the 1,519 agonist-triggered antagonist cycles.

Where this comes from:
47. Al-Inany HG, Youssef MA, Ayeleke RO, Brown J, Lam WS, Broekmans FJ. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2016;4(4):CD001750.
48. Youssef MAFM, Van der Veen F, Al-Inany HG, Mochtar MH, Griesinger G, Nagi Mohesen M, et al. Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist-assisted reproductive technology. Cochrane Database Syst Rev. 2014;2014(10):CD008046.
49. Zaat T, Zagers M, Mol F, Goddijn M, van Wely M, Mastenbroek S. Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database Syst Rev. 2021;2(2):CD011184.
56. Chen Z, Shi Y, Sun Y, Zhang B, Liang X, Cao Y, et al. Fresh versus frozen embryos for infertility in the polycystic ovary syndrome. N Engl J Med. 2016;375(6):523-533.
57. Shi Y, Sun Y, Hao C, Zhang H, Wei D, Zhang Y, et al. Transfer of fresh versus frozen embryos in ovulatory women. N Engl J Med. 2018;378(2):126-136.
50. Ludwig AK, Glawatz M, Griesinger G, Diedrich K, Ludwig M. Perioperative and post-operative complications of transvaginal ultrasound-guided oocyte retrieval: prospective study of >1000 oocyte retrievals. Hum Reprod. 2006;21(12):3235-3240.
51. Bodri D, Guillén JJ, Polo A, Trullenque M, Esteve C, Coll O. Complications related to ovarian stimulation and oocyte retrieval in 4052 oocyte donor cycles. Reprod Biomed Online. 2008;17(2):237-243.

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