L Rombauts1, R McMaster2, C Motteram3, S Fernando4. 1. Monash IVF, Epworth Hospital, 89 Bridge Rd, Richmond, Victoria 3121, Australia Hudson Institute of Medical Research, 246 Clayton Rd, Clayton, Victoria 3168, Australia Department of Obstetrics and Gynaecology, Monash University, 246 Clayton Rd, Clayton, Victoria 3168, Australia luk.rombauts@monash.edu. 2. Department of Obstetrics and Gynaecology, Monash University, 246 Clayton Rd, Clayton, Victoria 3168, Australia. 3. Monash IVF, Epworth Hospital, 89 Bridge Rd, Richmond, Victoria 3121, Australia. 4. Hudson Institute of Medical Research, 246 Clayton Rd, Clayton, Victoria 3168, Australia Department of Obstetrics and Gynaecology, Monash University, 246 Clayton Rd, Clayton, Victoria 3168, Australia.
Abstract
STUDY QUESTION: Is endometrial combined thickness (ECT) measured prior to embryo transfer (ET) associated with ectopic pregnancy (EP)? SUMMARY ANSWER: Following IVF, the risk of EP is 4-fold increased in women with an ECT of <9 mm compared with women with an ECT of >12 mm. WHAT IS KNOWN ALREADY: Known risk factors for EP include tubal damage, maternal cigarette smoking and endometriosis. EP is also more common following IVF but the underlying causes for this remain unclear. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study restricted to all IVF cycles leading to a pregnancy (βhCG > 50 IU/l) between January 2006 and December 2014. A total of 6465 patients achieved a pregnancy in 8120 cycles. Cycles using preimplantation genetic screening or donor oocytes were excluded. PARTICIPANTS/MATERIALS, SETTING, METHODS: This cohort consists of 6465 patients achieving a pregnancy in 6920 stimulated cycles with fresh embryo transfers (STIM ET) and 1200 hormone replacement therapy frozen embryo transfers (HRT-FET) cycles at a private IVF unit (Monash IVF, Melbourne, Australia). ECT was the primary independent variable of interest; the primary outcome was a diagnosis of EP. The dataset was analysed using binary logistic general estimating equations (SPSS v22.0) to calculate odds ratio (OR) for EP adjusted for known confounders (aOR). There was no loss to follow-up in the dataset. MAIN RESULTS AND THE ROLE OF CHANCE: The study groups did not differ significantly prior to IVF treatment. After adjusting for confounders, ECT remained statistically significant as an independent risk factor for EP. Compared with women with an ECT of <9 mm, women with an ECT of 9-12 mm had an aOR of 0.44 (95% CI 0.29-0.69, P < 0.01) and women with an ECT > 12 mm had an aOR of 0.27 (95% CI 0.10-0.77, P = 0.01). These differences remained statistically significant after performing a sensitivity analysis excluding HRT-FET, smokers and patients with tubal infertility. LIMITATIONS, REASONS FOR CAUTION: The study design is retrospective, and it is possible that not all confounders have been accounted for. Measurement of ECT was performed by highly trained sonographers, but some inconsistency between individuals may be present. WIDER IMPLICATIONS OF THE FINDINGS: Our group has previously demonstrated an increased risk of placenta praevia with increased ECT. These new findings suggest that the directionality of the uterine peristalsis waves matters more than their frequency or amplitude. Combining the data from both studies we now hypothesize that increased ECT is a marker for increased fundus-to-cervix uterine peristalsis, explaining both the increased placenta praevia risk and the lower EP risk. Further prospective studies are required to confirm these observations.
STUDY QUESTION: Is endometrial combined thickness (ECT) measured prior to embryo transfer (ET) associated with ectopic pregnancy (EP)? SUMMARY ANSWER: Following IVF, the risk of EP is 4-fold increased in women with an ECT of <9 mm compared with women with an ECT of >12 mm. WHAT IS KNOWN ALREADY: Known risk factors for EP include tubal damage, maternal cigarette smoking and endometriosis. EP is also more common following IVF but the underlying causes for this remain unclear. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study restricted to all IVF cycles leading to a pregnancy (βhCG > 50 IU/l) between January 2006 and December 2014. A total of 6465 patients achieved a pregnancy in 8120 cycles. Cycles using preimplantation genetic screening or donor oocytes were excluded. PARTICIPANTS/MATERIALS, SETTING, METHODS: This cohort consists of 6465 patients achieving a pregnancy in 6920 stimulated cycles with fresh embryo transfers (STIM ET) and 1200 hormone replacement therapy frozen embryo transfers (HRT-FET) cycles at a private IVF unit (Monash IVF, Melbourne, Australia). ECT was the primary independent variable of interest; the primary outcome was a diagnosis of EP. The dataset was analysed using binary logistic general estimating equations (SPSS v22.0) to calculate odds ratio (OR) for EP adjusted for known confounders (aOR). There was no loss to follow-up in the dataset. MAIN RESULTS AND THE ROLE OF CHANCE: The study groups did not differ significantly prior to IVF treatment. After adjusting for confounders, ECT remained statistically significant as an independent risk factor for EP. Compared with women with an ECT of <9 mm, women with an ECT of 9-12 mm had an aOR of 0.44 (95% CI 0.29-0.69, P < 0.01) and women with an ECT > 12 mm had an aOR of 0.27 (95% CI 0.10-0.77, P = 0.01). These differences remained statistically significant after performing a sensitivity analysis excluding HRT-FET, smokers and patients with tubal infertility. LIMITATIONS, REASONS FOR CAUTION: The study design is retrospective, and it is possible that not all confounders have been accounted for. Measurement of ECT was performed by highly trained sonographers, but some inconsistency between individuals may be present. WIDER IMPLICATIONS OF THE FINDINGS: Our group has previously demonstrated an increased risk of placenta praevia with increased ECT. These new findings suggest that the directionality of the uterine peristalsis waves matters more than their frequency or amplitude. Combining the data from both studies we now hypothesize that increased ECT is a marker for increased fundus-to-cervix uterine peristalsis, explaining both the increased placenta praevia risk and the lower EP risk. Further prospective studies are required to confirm these observations.