Delay in IVF treatment up to 180 days does not affect pregnancy outcomes in women with diminished ovarian reserve

Abstract

STUDY QUESTION Will a delay in initiating IVF treatment affect pregnancy outcomes in infertile women with diminished ovarian reserve? SUMMARY ANSWER A delay in IVF treatment up to 180 days does not affect the live birth rate for women with diminished ovarian reserve when compared to women who initiate IVF treatment within 90 days of presentation. WHAT IS KNOWN ALREADY In clinical practice, treatment delays can occur due to medical, logistical or financial reasons. Over a period of years, a gradual decline in ovarian reserve occurs which can result in declining outcomes in response to IVF treatment over time. There is disagreement among reproductive endocrinologists about whether delaying IVF treatment for a few months can negatively affect patient outcomes. STUDY DESIGN, SIZE, DURATION A retrospective cohort study of infertile patients in an academic hospital setting with diminished ovarian reserve who started an IVF cycle within 180 days of their initial consultation and underwent an oocyte retrieval with planned fresh embryo transfer between 1 January 2012 and 31 December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS Diminished ovarian reserve was defined as an anti-Müllerian hormone (AMH) <1.1 ng/ml. In total, 1790 patients met inclusion criteria (1115 immediate and 675 delayed treatment). Each patient had one included cycle and no subsequent data from additional frozen embryo transfer cycles were included. Since all cycle outcomes evaluated were from fresh embryo transfers, no genetically tested embryos were included. Patients were grouped by whether their cycle started 1–90 days after presentation (immediate) or 91–180 days (delayed). The primary outcome was live birth (≥24 weeks of gestation). A subgroup analysis of more severe forms of diminished ovarian reserve was performed to evaluate outcomes for patients with an AMH <0.5 and for patients >40 years old with an AMH <1.1 ng/ml (Bologna criteria for diminished ovarian reserve). Logistic regression analysis, adjusted a priori for patient age, was used to estimate the odds ratio (OR) with a 95% CI. All pregnancy outcomes were additionally adjusted for the number of embryos transferred. MAIN RESULTS AND THE ROLE OF CHANCE The mean ± SD number of days from presentation to IVF start was 50.5 ± 21.9 (immediate) and 128.8 ± 25.9 (delayed). After embryo transfer, the live birth rate was similar between groups (immediate: 23.9%; delayed: 25.6%; OR 1.08, 95% CI 0.85–1.38). Additionally, a similar live birth rate was observed in a subgroup analysis of patients with an AMH <0.5 ng/ml (immediate: 18.8%; delayed: 19.1%; OR 0.99, 95% CI 0.65–1.51) and in patients >40 years old with an AMH <1.1 ng/ml (immediate: 12.3%; delayed: 14.7%; OR 1.21, 95% CI 0.77–1.91). LIMITATIONS, REASONS FOR CAUTION There is the potential for selection bias with regard to the patients who started their IVF cycle within 90 days compared to 91–180 days after initial consultation. In addition, we did not include patients who were seen for initial evaluation but did not progress to IVF treatment with oocyte retrieval; therefore, our results should only be applied to patients with diminished ovarian reserve who complete an IVF cycle. Finally, since we excluded patients who started their IVF cycle greater than 180 days from their first visit, it is not known how such a delay in treatment affects pregnancy outcomes in IVF cycles. WIDER IMPLICATIONS OF THE FINDINGS A delay in initiating IVF treatment in patients with diminished ovarian reserve up to 180 days from the initial visit does not affect pregnancy outcomes. This observation remains true for patients who are in the high-risk categories for poor response to ovarian stimulation. Providers and patients should be reassured that when a short-term treatment delay is deemed necessary for medical, logistic or financial reasons, treatment outcomes will not be affected. STUDY FUNDING/COMPETING INTEREST(S) No financial support, funding or services were obtained for this study. The authors do not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER Not applicable.

Unexplained infertility and expectant management in women aged 39 or above: is it acceptable to ask couples to wait one year before receiving IVF? A retrospective cohort study

“…Our study can be reassuring for patients in the age range considered, who are cared with expectant management of at least eleven months before IVF as we did not nd evidence that waiting has a negative in uence on their live birth rate. These ndings may also reassure couples who have experienced or will experience delays in accessing IVF treatments due to the COVID-19 pandemic, according to similar results reported by other groups [25].…”

“…More importantly, the clinical question is more often: can we delay treatment for a certain period of time without causing harm to the patient and perhaps have them conceive spontaneously? A recent retrospective study shows that in patients with reduced ovarian reserve a delay of no more than six months is not associated with worse IVF outcomes [25], but the chances of achieving pregnancy without IVF have not been investigated. So, our dilemma is still open.…”

Non-essential treatment? Sub-fertility in the time of COVID-19 (and beyond)

“…Considering that time is a key element in assisted reproduction, I believe in the importance of prioritising discussions on how to administer treatments during a health emergency over discussions on whether to administer treatments in these circumstances. While it has been reported that only a few months of delay may not necessarily affect the chances of success of fertility treatment ( Romanski et al., 2020 ), waiting times from initial diagnosis of sub-fertility to the start of fertility treatment can be lengthy. Additionally, it is unclear whether there will be further suspensions in the event of a sustained rise in infections.…”

Impact of COVID-19 pandemic on the psychological status of infertile patients who had in vitro fertilization treatment interrupted or postponed: a cross-sectional study

“…The authors reported that discontinuation of fertility treatment for even one month in the USA could result in 369 fewer women having live birth, due to the increase in patients' age during the shutdown (20). On the opposite, another study preliminary reported that in women with diminished ovarian reserve (AMH <1.1 ng/ml) there was no difference in the live birth rate among women who initiated their IVF cycle within 90 days of their first visit due to COVID-19 pandemic compared to women who did procedures 91-180 days after initial consultation (21). Although the psychological impact of ART delayed was not evaluated in the study, these latter results may be reassuring to women with poor ovarian reserve, who may feel particularly anxious and depressed to begin their treatment and become frustrated when unexpected delays occur, as demonstrated by the logistic regression analysis of our data.…”