IVM for expected high responders: balancing the effectiveness and safety: In Reply

Hum Reprod. Volume 34, Issue 10, October 2019, Page 2081 – 2019-09-27

H. N. A. Vu¹, B.W. Mol², L.N. Vuong¹

Published: 27 September, 2019

Sir,
We would like to thank Huang and Kuang for their interest in our study (Ho et al., 2019) comparing the effectiveness and safety of IVM versus IVF in women with a high antral follicle count (AFC).
Huang and Kuang question whether patients with AFC >24 were at high risk of ovarian hyperstimulation syndrome (OHSS). An AFC ≥24 has been associated with an 8.6% risk of OHSS in women undergoing IVF, which increased to 11% in the presence of polycystic ovary syndrome (Jayaprakasan et al., 2012). In addition, an AFC >14 has been shown to have high sensitivity and specificity for predicting ovarian hyper-response (Kwee et al., 2007). Our patients with an AFC >24 were therefore at increased risk of developing OHSS. Indeed, the prevalence of OHSS in the IVF arm of our study was 3.7% (11/311), higher than the normal population. More importantly, we directly compared IVM to IVF in the predefined population of women undergoing IVF with an AFC >24, and our results show a decrease in OHSS over the whole range of patients.
We agree with Huang and Kuang that, apart from IVM, there are other approaches to reducing the risk of OHSS, including the use of a gonadotrophin releasing hormone agonist (GnRHa) protocol and a freeze-all strategy. In our opinion, presence or absence of OHSS is the most important point, while timing/onset of OHSS is less relevant. In our study, 3/11 women (27%) had early onset OHSS while 8/11 (73%) had late onset. Although early OHSS is less severe than late OHSS (Royal College of Obstetricians and Gynaecologists, 2016), this does not imply that we only need to avoid late OHSS by using a freeze-all strategy.
The FSH starting dose in our study reflects the clinical practice at our center for patients with high AFC and was chosen by individual physicians based on patient age and BMI (150 IU/day in 76% of patients and 225 IU/day in 24%). We choose hCG-triggered patients and excluded those with a GnRHa trigger, because we wanted to assess strategies that allowed fresh embryo transfer.
While our study shows that IVM results in a lower cumulative pregnancy rate due to a lower number of available embryos, the lower drug costs of IVM could possibly outweigh this disadvantage. Indeed, the cost should include direct medical costs (including FSH consumption, number of hospital visits, ultrasounds, blood tests and examinations and complications), direct non-medical costs (duration of stimulation, and patients’ travel and accommodation expenses) and indirect costs (e.g. loss of income during treatment). We are now performing a formal cost-effectiveness analysis comparing IVM and IVF that takes into account these issues. In view of the above, our study shows that IVM should be considered for selected women with AFC >24 and may be a first-line option for these patients. Our ongoing randomized controlled clinical trial comparing IVM versus GnRHa-triggered IVF in women with an AFC>24 (Vuong et al., 2018) will bring more clarity on this issue.

Conflict of interest

B.W.M. is supported by a National Health Medical Research Council Practitioner Fellowship (GNT1082548) and reports consultancy for ObsEva, Merck and Guerbet. L.N.V. and V.N.A.H. have no conflicts of interest to declare.