Letters to the Editor
The effect of intercourse on pregnancy rates during assisted human reproduction Dear Sir, We find the paper by Tremellen et al. (2000) very interesting. It attempts to provide the answer to a question frequently asked by couples undergoing assisted reproduction technology (ART) procedures. This is the first large study to show that sexual intercourse around the time of embryo transfer, far from being harmful, may even be beneficial to embryo development. The multi-centre study involved couples (women aged 18–40 years) undergoing fresh or frozen embryo transfers. Two hundred frozen embryo transfer cycles from one Australian centre and 400 fresh cycles from two Spanish centres were recruited. A total of 302 couples were randomized to have intercourse around the time of embryo transfer, and 298 to abstain, (654 and 689 embryos transferred respectively). The outcome measures studied were implantation, total and clinical pregnancy rates. During fresh cycles of IVF or ICSI, the ovaries are usually enlarged and may be very tender around the time of embryo transfer, and most would find sexual intercourse too painful. Questionnaire accounts of compliance amongst the Spanish groups randomized to have sexual intercourse may, therefore, be unreliable. An objective way of ensuring compliance was to ask patients to have sexual intercourse within 2 days before embryo transfer, and perform a microscopic examination of wet endocervical and vaginal smears obtained at the time of embryo transfer for evidence of spermatozoa. Our second observation concerns how the power calculation was performed by the authors. This study (with a total of 1343 embryos transferred) may have had sufficient power to detect a minimum 50% increase in implantation rate, [i.e. from 7.7–11.5% relative risk (RR) of 1.5, with a cycle cancellation rate of 10%], but does not have the power to detect a RR of 1.5 in pregnancy rate as claimed by the authors. In fact, the authors would have required a total of 4000 cycles of treatment reaching the embryo transfer stage to detect an increase in clinical pregnancy rate from 16.5–19.4% (i.e. RR of 1.21, with an alpha error of 5% and power of 80%) (Dupont and Plummer, 1990). Implantation rate, defined as the number of viable embryos at the 6 week scan per 100 transferred embryos is not an ideal outcome measure of an ART programme. The clinical pregnancy, if not live birth rate, is of far more clinical significance (see Instruction to authors, Human Reproduction, Volume 16, 2001).
Conclusions Whereas this study’s findings on the effect of sexual intercourse on implantation rates can be considered valid, a much larger study is required to demonstrate the effect of sexual intercourse on clinical pregnancy rates. It is tempting, but unwise, to assume that the differences seen in clinical pregnancy rates in this study, which involves 600 cycles of treatment, would go on to reach statistical significance with an adequate sample
size. This size would however, be very difficult to achieve with a primary study. Perhaps the time has come for a systematic review and meta-analysis of pooled data on the topic. References Dupont, W.D. and Plummer, W.D. (1990) Power and sample size calculations, a review and computer program. Controlled Clinical Trials, 11, 116–128. Tremellen, K.P., Valbuena, D., Landeras, J. et al. (2000) The effect of intercourse on pregnancy rates during assisted human reproduction. Hum. Reprod., 15, 2653–2658.
Bolarinde Ola1, Nahed Hammadieh, Spyros Papaioannou, Masoud Afnan and Khaldoun Sharif Assisted Conception Unit, Birmingham Women’s Hospital, Edgbaston, Birmingham, B15 2TG UK 1To
whom correspondence should be addressed. E-mail:
[email protected]
Dear Sir, We thank Dr Ola and colleagues for their interest in our paper. We would like to take this opportunity to address the issues that they have raised. Firstly, Ola et al. (2001) are concerned that couples would not be able to have intercourse around oocyte collection because the ovaries are swollen by gonadotrophin stimulation, while pelvic trauma caused by transvaginal oocyte collection may also make intercourse uncomfortable (Ola et al., 2001). While we agree that this can be the case, not all couples find intercourse painful during a fresh embryo transfer cycle. We do not advocate that couples must engage in intercourse during IVF treatment, but rather we believe that couples should be informed that it is quite safe for them to do so and that intercourse may even increase their chances of pregnancy. If a couple feels uncomfortable about having intercourse, either for physical or psychological reasons, they should be encouraged to abstain. One of the main aims of our study was to assess if intercourse is safe during an embryo transfer cycle, thereby giving couples choice, rather than encouraging strict abstinence as many clinics do. When couples undergoing infertility treatment are interviewed about issues related to treatment satisfaction, they identify informed choice and a sense of personal control as major factors influencing a positive outlook towards infertility treatment (Halman et al., 1993). The results of our paper give patients a choice. It has been suggested that by not performing endocervical smears for spermatozoa, we are unable to confirm compliance with the trial study allocations. While we accept that this may have been useful, we decided against it because patients may have perceived such a ‘compliance check’ as being too intrusive. In addition, in our study the assessment of cervical sperm numbers would not have been a perfect assessment of recent coital activity since almost half the couples had male type infertility. Azoospermic or severely oligospermic men may have produced a negative post-coital result even if intercourse had occurred. 2029
Letters to the Editor
Dr Ola and colleagues criticise our use of embryos transferred rather than treatment cycles for assessment of power calculations. They also disagree with our use of viable embryos (assessed at the 6 week ultrasound) instead of the more traditional livebirth rate. We used numbers of embryos transferred in our calculations because it enabled us to design a study of adequate statistical power within an achievable time frame. It was not possible for us to recruit the thousands of treatment cycles needed to achieve adequate statistical power in terms of pregnancy rates per treatment cycle. We agree that clinical pregnancy rates are the most significant outcome variable when assessing ART outcome, however our hypothesis was that exposure to semen through intercourse may have effects (positive, negative or neutral) on early embryo development and implantation events. We are sure that Dr Ola and colleagues would agree that assessment of viable embryo numbers at 6 weeks is a reasonable outcome measure of early embryo development. It is less biologically plausible that acute exposure to semen/intercourse around the time of embryo transfer is going to have an effect on fetal development in the second or third trimester. We hope that this study will encourage further investigation on the impact of infertility treatment on human sexuality and the impact of sexual practices on ART outcome. Further studies would then enable a meaningful systematic review or metaanalysis to be performed, as suggested by Dr Ola and colleagues. References Halman, L.J., Abbey, A. and Andrews, F.M. (1993) Why are couples satisfied with infertility treatment? Fertil. Steril., 59, 1046–1054 Ola, B., Hammadieh, N., Papaioannou, S. et al. (2001) The effect of intercourse on pregnancy rates during assisted human reproduction. Hum. Reprod., 16, 2023.
Kelton Tremellen1 and Robert Norman Reproductive Medicine Unit, Adelaide University, The Queen Elizabeth Hospital, Woodville, South Australia 5011, Australia 1To
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whom correspondence should be addressed
