NEWS: Study Highlights Association between Poor Response to Ovarian Stimulation and Higher Miscarriage Risk in IVF Cycles

Analyzing data from the Human Fertilization and Embryology Authority (HFEA) involving 124,351 IVF pregnancies, a UK study reported that the number of oocytes retrieved is strongly linked to clinical miscarriage rate. The study findings, which suggest the probable association between poor ovarian response and reduction in oocyte quantity and quality, are published in the latest edition of Human Reproduction.

Sesh Kamal Sunkara from the Division of Women’s Health, King’s College, London, UK, and coworkers evaluated the anonymous data from the statutory ART regulator in the UK, collected between 1991 and 2008, that included 420,185 stimulated fresh IVF cycles. In order to investigate the pregnancy outcomes, the study shortlisted the ART information only from those women who had at least one oocyte retrieved. The probability of the decrease in miscarriage rate, at or beyond the 3 cut-off points (4, 10, and 15 oocytes), was determined using stepwise logistic regression. The increase in the number of oocytes was linked to a reduction in miscarriage rate from 20% to 13%, prior to levelling off. However, there was no reduction in the miscarriage rate when >20 oocytes were retrieved. The risk of miscarriage was found to be lowest (9.9%) in women <38 years, with primary infertility not having a female cause, and who produce >3 oocytes.

The researchers concluded that poor response to ovarian stimulation was associated with an increased risk of clinical miscarriage. The results also indicated that miscarriage risk was more in patients with secondary infertility, advanced age, and female cause of infertility, when compared to male factor infertility, unexplained infertility, and younger age. Two of the limitations of the study that were pointed out were that no data was collected on total gonadotropin consumption, although the study involved only stimulated IVF cycles, and confounders like BMI were not considered, even though others such as age and infertility type were included.

Numerous studies have elucidated that decrease in oocyte quantity manifests as poor ovarian response. The main reason attributed to high miscarriage rate in women of advanced reproductive age is reduction in oocyte quality. Both oocyte quantity and quality decline with ovarian ageing, but there is a lack of consensus whether these two are inter-related. In order to ascertain this, miscarriage rates were compared in IVF cycles between poor responders and women with normal response in a Danish retrospective study by Haadsma et al (Reproductive BioMedicine Online, 2010). The scientists compared women who were successful in achieving pregnancy in their first complete IVF cycle (n= 1468) with patients who had miscarriages (n=367).

A statistically significant link was observed between poor response (<4 retrieved oocytes) and miscarriage (P=0.001); greater association being noted with advancing female age. Based on the findings, it was concluded that poor responders who were≥36 years had enhanced risk of miscarriage in comparison to normal responders (P=0.001); thereby, indicating the link between oocyte quality and quantitative ovarian reserve.

Reiterating the same findings, the American Society for Reproductive Medicine (ASRM), in a factsheet, ‘Risks of IVF’, highlighted that the risk of miscarriage increases with the mother’s age. The ASRM found similar rates of miscarriage in both natural conception and those undergoing IVF, with around 15% in women aged in their 20s to >50% in patients over 40 years.

As per the researchers of the current study, the findings have broader implications in minimizing the emotional and financial trauma of miscarriage after IVF, since the uncovering of the association between the number of oocytes retrieved and oocyte quality may aid in treatment planning, in terms of deciding to opt for another IVF cycle or oocyte donation. Additionally, this could facilitate in improving patient education and counselling of couples seeking IVF, especially regarding the link between poor ovarian response and increased miscarriage risk.

References

  • Sunkara SK, Khalaf Y, Maheshwari A, Seed P, Coomarasamy A. Association between response to ovarian stimulation and miscarriage following IVF: an analysis of 124 351 IVF pregnancies. Hum Reprod. 2014 Mar 20. [Epub ahead of print].
  • Haadsma ML, Groen H, Mooij TM, et al. Miscarriage risk for IVF pregnancies in poor responders to ovarian hyperstimulation. Reprod Biomed Online. 2010 Feb;20(2):191-200.
  • Risks of In Vitro Fertilization (IVF): ASRM Patient Fact Sheet. ASRM. Accessed May 16, 2014.
  • Miscarriage risk increases for women who respond poorly to IVF ovarian stimulation [press release]. UK:University of Birmingham; March 20, 2014. Accessed May 16, 2014.

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