Thin endometrial lining: is it more prevalent in patients utilizing preimplantation genetic testing for monogenic disease (PGT-M) and related to prior hormonal contraceptive use?

study questionIs a thin endometrial lining before ovulation triggering more prevalent in patients utilizing preimplantation genetic testing for monogenic disease (PGT-M) compared to the regular IVF/ICSI population and is this associated with prior hormonal contraceptive use? SUMMARY ANSWER: Thin (<8 mm) endometrial lining is more prevalent in PGT-M patients compared to the regular IVF/ICSI population and is associated with both longer prior hormonal contraceptive use and a shorter cessation interval of hormonal contraceptives before IVF/ICSI treatment. WHAT IS KNOWN ALREADY: Thin endometrial lining has been associated with lower pregnancy rates in IVF/ICSI cycles and increased chances of miscarriage and low birth weight. Endometrial thinning and atrophy occur during hormonal contraceptive use. Patients utilizing PGT-M typically use hormonal contraceptives up until treatment to avoid the risk of conception of a genetically affected child. Whether this could negatively affect endometrial thickness achieved during subsequent IVF/ICSI cycles is not known. STUDY DESIGN, SIZE, DURATION: A retrospective case control study was performed, including all PGT-M patients attending the University Medical Centre Groningen (cases), between 2009 and 2018. The control group consisted of two non-PGT IVF/ICSI patients for each PGT-M patient, matched for age and treatment period. PARTICIPANTS/MATERIALS, SETTING,

methodsFirst cycles of 122 PGT-M patients and 240 controls were included. Cessation interval of hormonal contraceptives was categorized as late cessation (cessation <1 year prior to treatment) or early cessation (>1 year prior to treatment). Endometrial thickness was routinely measured on the day of hCG triggering or 1 day prior. The prevalence of an endometrial lining <8 mm was compared between PGT-M patients and controls. Hormonal contraceptive use (both duration and cessation interval) was compared between both groups. Univariable and multivariable regression analyses were performed to identify risk factors for thin endometrial lining. In addition, cycle and pregnancy outcomes were compared within control/PGT-M groups between patients with endometrial lining > or <8 mm. MAIN RESULTS AND THE ROLE OF CHANCE: Thin endometrial lining on the day of hCG triggering was found significantly more often in the PGT-M group, compared to controls: 32% vs 11% (mean difference 21.0%, 95% CI: 11.7, 30.3%). As expected, more patients in the PGT-M group ceased their hormonal contraception late (<1 year): 64% vs 2% in the control group (mean difference 61.9%, 95% CI: 53.0, 70.8%). Average duration of hormonal contraceptive use was 10.6 years in the PGT-M group vs 9.3 years in controls (mean difference 1.3 years, 95% CI: 0.2, 2.3 years). Multivariable logistic regression analysis identified late cessation (OR: 6.0, 95% CI: 1.9-19.2) and duration of prior hormonal contraceptive use (OR per year increase 1.1, 95% CI: 1.0-1.2) as significant independent risk factors for a thin endometrial lining. In relation to outcome, we found a statistically significant increase in miscarriage rate in PGT-M patients with an endometrial lining <8 mm compared to those with an endometrial lining >8 mm (20.0% vs 1.7%, mean difference 18.3%, 95% CI: 2.3, 34.3%). A trend towards lower birth weight and gestation- and gender-adjusted birth weight (z-score) was also found in this group. No statistically significant differences were detected in pregnancy rate, live birth rate, or incidence of preterm delivery or SGA. Within the control group, no statistically significant differences were found in outcomes between patients with an endometrial lining <8 compared to an endometrial lining >8 mm. LIMITATIONS, REASONS FOR CAUTION: The study is retrospective. Various types of hormonal contraceptives were reported which possibly exert different effects on the endometrial lining. In relation to pregnancy outcome measures, numbers were very limited; therefore, no firm conclusions should be drawn. WIDER IMPLICATIONS OF THE

findingsThis study provides further insight into the role of prior hormonal contraceptive use as a possible contributor to the occurrence of thin endometrial lining during ART treatment. Future studies should provide more information on its clinical relevance, to determine whether PGT-M patients can be reassured, or should be counselled to stop hormonal contraceptive use and change to an alternative contraceptive method prior to PGT treatment. STUDY FUNDING/COMPETING INTERESTS: No specific funding was used and no conflicts of interests are declared. TRIAL REGISTRATION NUMBER: N/A.