The increased prevalence of multiple births associated with assisted reproduction technology (ART) can be largely attributed to the widespread use of ovulation induction medications and multiple embryo transfer. Now, a research study published in the recent issue of the journal Fertility and Sterility has suggested less aggressive stimulation as an effective strategy to reduce high-order multiple births (HOMB) due to ovulation induction (OI).
Richard Palmer Dickey, from the Department of Obstetrics and Gynecology, Louisiana State University School of Medicine, New Orleans, Louisiana, conducted the retrospective analysis to evaluate HOMB-related factors due to ovarian induction and assess the efficacy of various strategies employed for lowering its occurrence.
The study results showed a positive association between high-order multiple pregnancy (HOMP), and administration of estradiol (E2), high doses of gonadotropin, and the number of preovulatory follicles of 7-10 mm. However, an inverse relation was noted between HOMP, and number of treatment cycles and the patient’s age. The study found that strategies such as, minimal doses of gonadotropin, clomiphene use prior to gonadotropin administration, aspiration of excess follicles, and cancellation of over three follicles of >10-15 mm in size, were successful in lowering HOMP. The researcher also suggested that pregnancy rate per patient need not be affected by the administration of low-dose gonadotropin if prolonged for 4-6 cycles. Based on the study results, the researcher concluded that less aggressive ovarian stimulation may aid in reducing HOMPs due to OI to 2% or less, without affecting the patient’s overall chances of pregnancy.
In 1998, the Society for Assisted Reproductive Technology/American Society for Reproductive Medicine (SART/ASRM) Practice Committee put forth certain guidelines to aid ART programs in determining suitable number of embryo transfers, in its efforts to minimize the chances of HOMB. Earlier, the same researcher (Fertility and Sterility, 2007) analyzed the efficacy of the recommendations in reducing HOMB due to OI and ART.
The analysis of US natality files, and Centers for Disease Control and Prevention (CDC) and ASRM/SART registries revealed that, between the period 1998 and 2003, there was no change in the number of HOMB; however, there was a 17% increase in the number of twin births. Also, from 1998, data showed a 67% and 65% corresponding increase in total births due to ART and twin birth rate, with a 8% and 35% decrease in triplet births and quadruplet/+ births, respectively. Also, the comparative ratio between twin, triplet, and quadruplet/+ births to total ART births ratio showed a corresponding decrease of 2%, 45%, and 61%. The estimated percentages of multiple births due to ART and OI under different categories in the year 2003 were 16% and 21% of twins, 45% and 37% triplets, and 30% and 62% quadruplets/+, respectively. The study results concluded that there was a substantial decrease in the ratio of HOMB births to total ART births, following the release of the SART/ASRM recommendations. However, due to rise in total ART births (67%) and triplet births from OI, there was no decrease in the number of HOMB in the US.
Preterm birth, low birth weight, congenital abnormalities, fetal and infant mortality, and prolonged morbidity and disability among survivors are major adverse outcomes associated with multiple pregnancies. It may also enhance the risk for obstetric complications including prenatal screening problems, preeclampsia and eclampsia, preterm delivery, antepartum haemorrhage, intrauterine growth retardation, surgery or assisted delivery. With the adoption of effective strategies for the reduction of multiple pregnancies during ART, such as less aggressive ovarian stimulation, assisted techniques may result in better clinical outcomes with minimal associated risks for both mother and offspring.
References
1. Dickey RP. Strategies to reduce multiple pregnancies due to ovulation stimulation. Fertil Steril. 2009 Jan;91(1):1-17. Epub 2008 Oct 29.
2. Dickey RP. The relative contribution of assisted reproductive technologies and ovulation induction to multiple births in the United States 5 years after the Society for Assisted Reproductive Technology/American Society for Reproductive Medicine recommendation to limit the number of embryos transferred. Fertil Steril. 2007 Dec;88(6):1554-61.
