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How Can We Reduce the Risk of OHSS?

Debate continues whether severe OHSS can be prevented (1). Since the advent of gonadotropin ovulation induction more than 40 years ago patients have suffered potentially life threatening consequences of therapy in an attempt to conceive. ART, while controlling the number of embryos that eventually have the possibility to implant, has ushered in more aggressive stimulation protocols with greater potential to overstimulate the ovaries. Risk factors for severe OHSS include high estradiol levels, prior ‘high response’ with gonadotropins, luteal phase stimulation with hCG, multiple follicles, PCOS, polycystic appearance of the ovaries, and pregnancy (2). Strategies may be used to minimize the risk of OHSS in ART cycles include the choice of stimulation protocol and luteal phase support protocol, as well as therapies directed at several of the potential mediators.

Natural cycle IVF all but eliminates OHSS. It is amazing that the pregnancy rates 25 years ago were approximately 20 % when these protocols were used commonly. This type of stimulation had lower pregnancy rates than seen today, but still they are acceptable. Drawbacks include premature ovulation, difficulty scheduling, and the potential not to retrieve an egg. Clomiphene and Clomiphene/hMG protocols have also been used as more ‘gentle stimulations’ (3). The use of lower doses of gonadotropins or a step down- approach to stimulation where the smaller follicles are essentially starved of stimulation may potentially be more gentle as well. The use of a lower dose of hCG, 5000 IU instead of 10,000 IU may be worthwhile, as well as delay of hCG if the peak estradiol level is above 2000 pg/ml. Recombinant LH, which has a much shorter t1/2 life than HCG may cause less OHSS yet still induce final oocyte maturation. GnRH agonists have been used to induce oocyte maturation and may have less OHSS associated with its use, but this may not work in already down-regulated cycles which are common in IVF (4). More recently, GnRH antagonists, which promptly suppress LH, have been shown to have a lower risk of OHSS (5). Another commonly used strategy is to ‘coast’, that is withhold gonadotropin stimulation until the estradiol level drops to below 2000 pg/ml. There is a risk of poor oocyte quality (6), however. Another option is to retrieve all of the oocytes and cryopreserve at the pronuclear stage on day #1 (7). While the patients my be unhappy with the lack of a transfer, in the long run the danger of OHSS may be avoided. Once HCG has been administered, some have given intravenous albumin prophylactically in order to help maintain intravascular volume and potential decrease the vascular permeability(8), a finding not reported by all (9,10). Recently, steroid ovarian suppression has been shown to have lower incidence of OHSS (11). While we may never completely remove the risk of OHSS, close attention to prevention will serve our patients well.

References:

1. Kol S, Itskovitz-Eldor J. Severe OHSS, yes there is a strategy to prevent it. Hum. Reprod. 2000, 15(11):2266-2267.

2. Paulson R. Prevention and treatment of ovarian hyperstimulation. Presented at 15th annual IVF and embryo transfer comprehensive update. (UCLA School of Medicine), Santa Barbara, July 14-17, 2002.

3. Olivennes F. More drugs, more problems, more multiples; Do we need ‘friendlier’ IVF? Presented at the 15th annual IVf and embryo transfer comprehensive update. (UCLA School of Medicine). Santa Barbara, July 14-17, 2002.

4. Lewit N, Kol S, Manor D, Itskovitz-Eldor J. Comparison of gonadotropin-releasing hormone analogues and human chorionic gonadotrophin for the induction of ovulation and prevention of ovarian hyperstimulation syndrome: a case-control study. 1996, Hum. Reprod. 11:1399-1402.

5. Ludwig M, Felberbaum RE, Devroey P, Albano C, Reithmuller-Winzen H, Schuler A, Engle W, Diedrich K. Significant reduction in the incidence of ovarian hyperstimulation syndrome (OHSS) using the LHRH antagonist cetrorelix in controlled ovarian hyperstimulation for assisted reproduction. 2000. Arch. Gynecol. Obstst. 264:29-32.

6. Benadiva C, Davis O, Kligman I, Manjy M, Jiu HC, Rosenwaks Z. Withholding gonadotropin administration is an effective alternative for the prevention of ovarian hyperstimulation syndrome. 1997. Fert. Steril. 67:724-7

7. Feraretti AP, Gianaroli L, Magli C, Fortini D, Selman HA, Feliciani E. Elective cryopreservation of all pronucleate embryos in women at risk of ovarian hyperstimulation syndrome:efficiency and safety. Hum. Reprod. 14: 1457-60.

8. Asch RH, Ivery G, Goldsman M, Frederick JL, Staone SC, Balmaceda JP. The use of intravenous albumin in patients at high risk for severe ovarian hyperstimulation syndrome. 1993. Hum. Reprod. 8:1015-20.

9. Belver J, Munoz EA, Ballesteros A, Soares SR, Bosch E, Simon C, Pellicer A, Remohi J. Intravenous albumin does not prevent moderate-severe ovarian hyperstimulation syndrome in high-risk IVF patients: a randomized controlled study. 2003. Hum. Reprod. 18(11): 2283-88.

10. Mukherjee T, Copperman AB, Sandler B, Bustillo M, Grunfeld L. Severe ovarian hyperstimulation despite prophylactic albumin at the time of oocyte retrieval for in vitro fertilization and embryo transfer. 1995. Fertil. Steril. 64: 641-3.

11. Schwarzler P, Abendstein BJ, klingler A, Kreuzer E, Rjosk HK. Prevention of severe ovarian hyperstimulation syndrome (OHSS) in IVF patients by steroid ovarian suppression- a prospective randomized study. 2003. Hum. Fertil. 6(3);125-9.
 

 

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