Hum. Reprod. Advance Access published January 29, 2016 Human Reproduction, Vol.0, No.0 pp. 1 –1, 2016

LETTER TO THE EDITOR

Every cycle counts

References Kasius A, Smit JG, Torrance HL, Eijkemans MJ, Mol BW, Opmeer BC, Broekmans FJ. Endometrial thickness and pregnancy rates after IVF: a systematic review and meta-analysis. Hum Reprod Update 2014;20:530–541. Mol BW, Ankum WM, Bossuyt PM, Van der Veen F. Contraception and the risk of ectopic pregnancy: a meta-analysis. Contraception 1995; 52:337 – 341. Rombauts L, McMaster R, Motteram C, Fernando S. Risk of ectopic pregnancy is linked to endometrial thickness in a retrospective cohort study of 8120 assisted reproduction technology cycles. Hum Reprod 2015;30:2846 – 2852. Searle SE. The intrauterine device and the intrauterine system. Best Pract Res Clin Obstet Gynaecol 2014;28:807– 824. Rui Wang* and Ben W. Mol Robinson Research Institute, The University of Adelaide, 72 King William Road, Adelaide, SA 5000, Australia *Correspondence address. E-mail: [email protected] doi:10.1093/humrep/dew001

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Sir, We read with interest the retrospective cohort study published in the journal by Rombauts and colleagues (Rombauts et al., 2015). The authors reported on the association between endometrial combined thickness (ECT) measured prior to embryo transfer and the risk of ectopic pregnancy (EP). They concluded that a thin ECT is an independent risk factor for developing EP following assisted reproduction. We are afraid that the fact that the authors ignore non-pregnant cycles has misinformed their conclusion. If we take the perspective of an embryo at the moment of transfer, then there is a probability of intrauterine and a probability of ectopic nidation. While the probability of EP is the topic of study, the probability of intrauterine nidation is dependent on ECT. A recent review showed that a thin endometrium in an IVF cycle reduces pregnancy chances (Kasius et al., 2014). Thus, when the denominator is established only from cycles in which women got pregnant, the lower risk of intrauterine pregnancy (IUP) in women with thin endometrium will inflate the EP rate, while the probability of ectopic nidation as such is actually independent on endometrial thickness. A similar problem occurred when studying the association between intrauterine device (IUD) and EP risk (Mol et al., 1995). When an IUD fails and a woman conceives with an IUD in situ, the chance of the pregnancy being ectopically nidated is 10%. However, the absolute risk of EP with IUD is low (around 0.02 per 100 woman years), 20 times less than for women using no contraception (Searle, 2014). Thus we cannot conclude that an IUD is a risk factor of EP. In contrast, IUD protects against EP, but it protects even stronger against IUP.

In the recent systematic review and meta-analysis that assessed the clinical significance of ECT, ectopic pregnancy was considered as a secondary outcome (Kasius et al., 2014). However, none of the included studies reported EP. We suggest to Rombauts et al. to repeat their study using all women undergoing embryo transfers as the denominator, rather than those who achieved pregnancy alone. Only in that case we will be able to assess whether increased ECT is a marker for increased fundus-to-cervix uterine peristalsis, as the authors hypothesize.

Every cycle counts.

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