Based on the available data, IVM eliminates severe OHSS in patients who are candidates for IVM. If one views the primary benefit of IVM as its ability to reduce the incidence of OHSS, then it is worthwhile to try to understand what burden OHSS presents for IVF. At present, IVM is primarily used for patients with ovulatory PCO and anovulatory PCO (PCOS) [21–24, 29–31]. In 2006, Heijnen et al. published a meta-analysis of case-control studies of IVF cycles in patients with and without PCOS [6]. They found nine studies meeting their criteria, but these uncommonly provided information on cycle cancellations for hyper-response or on the incidence of OHSS. Overall cycle cancellation (for any reason) was four times as frequent for PCOS patients than for non-PCO patients. Three studies provided information on OHSS. In one study, two patients (11%) were hospitalized for moderate to severe OHSS. The second study reported a 16.9% incidence of mild to moderate OHSS and a 3.9% incidence of severe OHSS. The third study reported two cases of OHSS in PCOS patients and one case in a non-PCO patient. At best, we conclude that OHSS is not uncommon in IVF patients with PCOS. Again, our understanding of the factors influencing the development of OHSS and the differences between IVM and IVF suggests that OHSS should not occur with IVM in patients with PCOS. IVM also prevents the discomfort that patients feel due to mild OHSS after IVF. The number of such patients involved is even harder to quantify, but avoiding pain and discomfort in patients is a routine part of good medical care.

Diverse management approaches or treatments for patients either known to be at high risk for OHSS before the start of an IVF cycle or who become high risk for OHSS in the course of an IVF cycle have been advocated. Some of the patients who become high risk for severe OHSS during a cycle are managed by cycle cancellation prior to oocyte aspiration and they incur considerable wasted expense in terms of medications, monitoring costs, and time missed from work. In 2012, more than 2400 women in the USA under age 35 had cycles cancelled prior to oocyte aspiration [8]. At least some of these cancellations were due to OHSS risk. In an ESHRE questionnaire survey, up to 20% of IVF physicians would manage patients having very high estradiol levels by cycle cancellation [1]. In a Web-based Internet study, 18% of physicians from 262 centers and 68 nations would also manage a patient with a very high risk of severe OHSS by cycle cancellation [32].

There are several treatments to mitigate or prevent the development of severe OHSS that are widely used. They are not as effective as IVM because they are less effective in modifying the impact of VEGF on the patient (Table 23.2). Most of these interventions impose extra burdens on patients that they would not experience with IVM (Table 23.3).

The most effective of these (after IVM) is using a GnRH agonist to trigger oocyte maturation. GnRH agonists produce an LH surge that is shorter in duration than a physiological surge. This LH spike is adequate to promote oocyte maturation, but not adequate to establish a corpus luteum. Early luteolysis eliminates the period of highest production of VEGF and also prevents late-onset OHSS since there is no corpus luteum to be rescued. Some of this benefit may be lost with the concomitant use of low doses of hCG, which may be used with a GnRH agonist trigger to improve the pregnancy rate. This is because the half-life of hCG is much longer than that of LH, and hCG activates the VEGF system more effectively than does LH [33, 40]. Table 24.​4 is a sample listing of reports in the literature of OHSS occurring in cycles utilizing a GnRH agonist to trigger oocyte maturity. One may hypothesize that these episodes of OHSS are due to severe OHSS occurring prior to the use of GnRH agonist, an atypical response by the patient to GnRH agonist, a confounding effect of low-dose hCG use, or a genetic mutation of the FSH or VEGF receptor. Similar to IVM for which a corpus luteum is not present, when a GnRH agonist is used, the luteal phase and early pregnancy need to be managed with supplemental estrogen and progesterone (Table 23.4).