Oocyte Yield Predicts OHSS in IVF Treatments

Oocyte Number as a Predictor for Ovarian Hyperstimulation Syndrome and Live Birth: An Analysis of 256,381 In Vitro Fertilization Cycles

Steward RG, Lan L, Shah AA, et al
Fertil Steril. 2014;101:967-973

Background

In vitro fertilization (IVF) has been practiced for over 35 years. It is estimated that in 2005, more than 1 million cycles were performed worldwide.^[1] In the developed world, up to 5% of children are conceived in vitro.^[2]

The average age of women at first birth has consequently increased, and in many countries it is already over 30 years.^[3] Owing to this trend and the decline in number and quality of oocytes with advanced age, we can expect to see an increase in the number of couples with fertility problems in the upcoming years, and there will be a need for even more IVF treatments.

For the most part, IVF is a safe procedure and eventually results in a positive outcome for the majority of couples. However, just like any other intervention, IVF also carries risks. The use of stimulation is associated with an increased thromboembolic risk; sedation and retrieval are associated with surgical risks; and the possibility of long-term adverse outcomes cannot be ruled out, although the current data are fairly reassuring.^[4,5,6]

There are 2 more common adverse outcomes of IVF. Although the continuously decreasing number of transferred embryos has led to a reduction of high-order multiple gestations, little impact on twin pregnancy rates has been seen so far. A twin pregnancy carries more maternal and neonatal risks than a singleton pregnancy. In addition, use of stimulation as part of the procedure is associated with risk for ovarian hyperstimulation syndrome (OHSS), the most severe iatrogenic complication of IVF.^[7]

Therefore, we need to plan treatments that maximize the chance of success while maintaining risks at a very low level. This study assessed how egg yield is associated with OHSS risk and treatment outcome.

The Study

This report is based on data obtained from the Society for Assisted Reproductive Technologies registry for 2008-2010. Researchers were able to analyze 256,381 cycles with known egg yield. Egg yield was categorized as 0-5 (18.4%), 6-10 (29.5%), 11-15 (24%), 16-20 (14.5%), 21-25 (7.4%), and > 25 (6.2%). Pregnancy rate, live birth rate, and OHSS incidence were compared among the groups.

The live birth rate increased as more eggs were collected, up until 11-15 oocytes (0-5 oocytes, 17%; 11-15 oocytes, 39.3%). The odds of live birth were significantly reduced in the lower egg categories compared with the 11- to 15-egg group. There was, however, no further significant increase in live birth rates in the higher oocyte yield groups.

The risk for OHSS was below 1% in the < 15-egg groups and over 6% in the > 25-egg group. The increase in the risk for OHSS was significant in the higher egg yield groups compared with the < 15-oocyte groups.

Receiver-operating characteristic analysis determined 15 oocytes as a cut-off value above which OHSS risk significantly increased (71.1% sensitivity, 72.4% specificity). Egg yield, however, could not precisely predict live birth.

The authors concluded that with > 15 oocytes collected, the risk for OHSS significantly increased but the pregnancy rate did not improve.

Viewpoint

OHSS is an iatrogenic complication of ovarian hyperstimulation. In response to the final trigger with human chorionic gonadotropin (used before oocyte collection), the synthesis of vasoactive substances (mainly vascular endothelial growth factor) is induced. These in turn increase the vascular permeability and shift fluid from the intravascular to the extravascular space.

Mild OHSS is characterized by ovarian enlargement and some abdominal discomfort, but the more severe cases can be fatal. In these cases, severe fluid and electrolyte imbalance may lead to renal failure, respiratory distress, and circulatory collapse. The risk for thrombosis increases as well.^[7]

Certain patient and cycle characteristics are associated with an increased risk for OHSS. The higher the number of eggs collected, the higher the risk. IVF, however, works best when several eggs are collected; stimulation, therefore, is an important part of treatment. One has to decide how many eggs to aim for in order to achieve optimal outcome while keeping risks at low levels.

Several groups have tried to answer this question. Sunkara and colleagues^[8] found a continuous increase in pregnancy rates up until 15 eggs and a plateau in the pregnancy rates beyond that, on the basis of over 400,000 cycles. Using a smaller sample size, van der Gaast and colleagues^[9] determined 13.1 as the optimal egg yield. The study discussed here drew similar conclusions.

Once the goal has been set, the stimulation protocol, drug type, and dose need to be determined. Ovarian function markers, body mass index, antral follicle count, age, and response to previous treatment can help with the treatment plan. Still, it is important for one to monitor the stimulation and make adjustments when needed, and even be prepared to cancel the cycle if things do not go in the right direction. Because there is no treatment (besides symptom relief) for OHSS, every effort should be made to avoid it.

Treatment individualization is an important part of IVF. It seems that an egg yield of around 15 provides optimal pregnancy and live birth rates while keeping the risk for OHSS at a very low level.

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