Embryo Freezing and OHSS: A Strategy for Risk Reduction
Breaking the temporal link between ovarian stimulation and embryo transfer
Michael B. Yakass, Ph.D 1,2
Introduction
Ovarian hyperstimulation syndrome (OHSS) remains one of the most serious iatrogenic complications of assisted reproductive technology (ART). Although advances in ovarian stimulation protocols and patient monitoring have significantly reduced its incidence, severe OHSS continues to pose health risks for women undergoing in vitro fertilization (IVF). A paradigm shift in the management of OHSS has emerged with the increasing use of embryo freezing (cryopreservation) as a proactive strategy to mitigate this risk.
By breaking the temporal link between ovarian stimulation and embryo transfer, clinicians can significantly reduce the risk of OHSS while preserving, and often enhancing, the chances of successful pregnancy.
Basic Mechanism of OHSS
OHSS is an exaggerated response to ovarian stimulation, characterized by enlarged ovaries and a fluid shift from the intravascular to the extravascular space, leading to ascites, hemoconcentration, and in severe cases, thromboembolism, renal failure, or even death. It typically manifests after the administration of human chorionic gonadotropin (hCG), used to trigger final oocyte maturation, or in early pregnancy when endogenous hCG levels rise.
High-risk patients include those with:
· Polycystic ovary syndrome (PCOS)
· High antral follicle count (AFC)
· Elevated anti-Mullerian hormone (AMH)
· History of OHSS
· Excessive follicular response to stimulation
The Role of Embryo Freezing in OHSS prevention or reduction
The conventional fresh embryo transfer approach, particularly when combined with hCG triggering, contributes significantly to late-onset OHSS occurring due to rising hCG from early pregnancy. The strategy of “freeze-all” or elective embryo cryopreservation especially when coupled with a gonadotropin-releasing hormone (GnRH) agonist trigger has transformed OHSS prevention (Devroey et al., 2011).
Numerous studies have confirmed the protective role of embryo freezing to the sequelae of OHSS. A number of meta-analyses have shown that freeze-all strategies can reduce OHSS incidence without compromising pregnancy outcomes (Marino et al., 2022).
Randomized controlled trials comparing fresh vs. frozen embryo transfer cycles in high responders show significantly reduced OHSS rates in the freeze-all arms, with comparable, if not improved implantation and live birth rates (Roque et al., 2019).
The strategy of “freeze-all” or elective embryo cryopreservation especially when coupled with a gonadotropin-releasing hormone (GnRH) agonist trigger has transformed OHSS prevention (Devroey et al., 2011)
The success of these strategies, however, hinges significantly on the method of freezing. Over the past decade, the transition from slow freezing to vitrification in IVF laboratories has revolutionized embryo survival and clinical outcomes.
Slow Freezing
Slow freezing, the traditional cryopreservation method, involves gradually cooling embryos in a controlled, staged process. This method uses low concentrations of cryoprotectants and aims to minimize ice crystal formation by allowing water to move out of the cells during slow cooling.
However, despite its clinical utility, slow freezing has notable limitations including:
· Lower post-thaw embryo survival rates especially in blastocysts, (Nagy et al, 2020)
· Reduced implantation and pregnancy rates compared to fresh transfers
· Longer processing time
· reliance on expensive, programmable freezers
The Vitrification Breakthrough
Vitrification is an ultra-rapid freezing technique that transforms the cellular contents of an embryo into a glass-like, ice-free solid state within seconds. This is achieved through:
· High concentrations of cryoprotectants.
· Immediate exposure to liquid nitrogen at -196°C.
· Use of minimal volume carriers (e.g., Cryotop or Cryoloop) for faster cooling rates.
Key Improvements with Vitrification
1. Superior Survival Rates
Vitrification has been shown to result in embryo survival rates exceeding 90%, compared to 50–70% with slow freezing. This is particularly true for blastocysts, which are more vulnerable to freezing damage due to their large fluid-filled cavity and complex cellular structure (Nagy et al., 2020).
2. Improved Implantation and Pregnancy Outcomes
Numerous clinical studies and meta-analyses report that vitrified embryos, especially when warmed properly, lead to implantation and live birth rates that are comparable to, or even better than, fresh transfers. This is a major advancement for elective embryo freezing protocols especially in cases where one wants to avoid an exacerbation in OHSS cases.
3. Faster, More Efficient Workflow
Vitrification eliminates the need for programmable freezers and long, staged freezing cycles. With proper training, embryologists can complete the freezing process within minutes, streamlining IVF lab operations.
4. Reduced Ice Crystal Formation
The ultra-rapid cooling rates of vitrification (over 10,000°C per minute) prevent the formation of damaging ice crystals, protecting the integrity of both cellular organelles and the cytoskeleton.
Challenges concerning vitrification
Despite its advantages, vitrification requires:
· Precise technique and training to avoid cryoprotectant toxicity and
· Strict time management to prevent osmotic shock.
Conclusion
Vitrification represents a major leap forward in reproductive technology, offering higher embryo survival rates, better clinical outcomes, and greater flexibility in patient care. By breaking the temporal link between ovarian stimulation and embryo transfer, clinicians can significantly reduce the risk of OHSS while preserving, and often enhancing, the chances of successful pregnancy. As IVF continues to evolve, the efficiency and reliability of vitrification will remain central to advancing success rates and ensuring patient safety—especially in risk-reduction strategies like freeze-all cycles to prevent OHSS.
QUIZ!!
References
Devroey P, Polyzos NP, Blockeel C. An OHSS-Free Clinic by segmentation of IVF treatment. Hum Reprod. 2011 Oct;26(10):2593-7. doi: 10.1093/humrep/der251. Epub 2011 Aug 9. PMID: 21828116.
Marino A, Gullo S, Sammartano F, Volpes A, Allegra A. Algorithm-based individualization methodology of the starting gonadotropin dose in IVF/ICSI and the freeze-all strategy prevent OHSS equally in normal responders: a systematic review and network meta-analysis of the evidence. J Assist Reprod Genet. 2022 Jul;39(7):1583-1601. doi: 10.1007/s10815-022-02503-2. Epub 2022 May 13. PMID: 35551563; PMCID: PMC9365921.
Roque M, Haahr T, Geber S, Esteves SC, Humaidan P. Fresh versus elective frozen embryo transfer in IVF/ICSI cycles: a systematic review and meta-analysis of reproductive outcomes. Hum Reprod Update. 2019 Jan 1;25(1):2-14. doi: 10.1093/humupd/dmy033. PMID: 30388233.
Nagy ZP, Shapiro D, Chang CC. Vitrification of the human embryo: a more efficient and safer in vitro fertilization treatment. Fertil Steril. 2020 Feb;113(2):241-247. doi: 10.1016/j.fertnstert.2019.12.009. PMID: 32106970.
Michael B. Yakass, Ph.D
1 The Fertility Centrum, 13 Nii Aku Ashong Street, Adjiringanor, East Legon – Accra.
2 West African Centre for Cell Biology and Infectious Pathogens (WACCBIP), University of Ghana, Accra, Ghana.