How effective is in vitro fertilization, and how can it be improved?

8 03 2011

To the Editor:

We would like to thank Dr. Stewart et al. for the fine article (1). The aim of the study was to determine in vitro fertilization (IVF) effectiveness in women undergoing IVF treatment at clinics in Western Australia between 1982-1992 and 1993-2002. They suggested that IVF effectiveness could be improved particularly in women over 35 who underwent more cycles.

How effective is IVF, and how can it be improved? The cumulative live birth rates in 20 years period; between 1982-1992 and 1993-2002 were analyzed and it has been reported that the increase in cumulative live birth must be due to increased IVF attempts in each patient. Can this improvement be related only to one factor? Must we ignore all of the developments in assisted reproductive technologies (ART) in a 20-year period?

The use of ART has increased over recent years with concomitant increases in success rates in part by the use of intracytoplasmic sperm injection (ICSI) for male infertility (2). The use of donor oocytes and a host uterus are other successful strategies for older women.

Salpingectomy prior to IVF increases live birth rate in patients with hydrosalpinx.

There are some other improvements in IVF, such as assisted embryo hatching, preimplantation genetic diagnosis, in vitro maturation and oocyte and ovarian tissue cryopreservation. Embryo cryopreservation and blastocyst transfer had positively associated with delivery rates in all ages (3,4). Outcomes of IVF pregnancies are seriously affected by multiple pregnancies. Both guidelines for embryo transfer and improvements in laboratory technology and neonatal intensive care unit ameliorate this problem.

Many factors that were not defined in the text, such as causes of infertility, duration of infertility, responsiveness to ovulation induction, different stimulation protocols, male infertility, embryo quality, the number of embryos transferred, and luteal phase support affect IVF outcome. In order to compare IVF outcomes in two groups in different time periods, all of the factors must be adjusted in each group. It would be better if the percentage of ICSI cycles, fresh or frozen embryo transfers, sperm or oocyte donation cycles in the groups were defined in the text. The authors only reported that 6% of deliveries in women aged 40-44 years were to donor recipients, but other variables were missing. Some factors such as the quality of the embryology laboratory and embryo transfer technique, which affect live birth rates, were also important in IVF outcome.

It would be also be better if other parameters of IVF outcome were defined, such as implantation rate, pregnancy rate and pregnancy loss. These parameters are important, because ongoing pregnancies are also affected by some other variables, such as smoking, alcohol intake, race, uterine abnormalities, underlying antiphospholipid syndrome, and inherited thrombophilias, that would unfortunately decrease the IVF success.

The number of cycles attempted was 2.6 in group 1 and 3.0 in group 2. Is there any statistical difference between the two groups? Were there any statistically different parameters between the groups in Table 1? We think the p values must also be defined in the study.

Fatma Ferda Verit, MD
Department of Obstetrics and Gynecology
Harran University, Faculty of Medicine
Sanliurfa, TURKEY

Ayhan Verit, MD
Department of Urology
Harran University, Faculty of Medicine
Sanliurfa, TURKEY

References
1. Stewart LM, Holman CD, Hart R, Finn J, Mai Q, Preen DB. How effective is in vitro fertilization, and how can it be improved? Fertil Steril 2011 Feb 11. [Epub ahead of print].

2. Palermo G, Joris H, Devroey P, Van Steirteghem AC (1992) Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet 340:17–18.

3. Stern JE, Goldman MB, Hatasaka H, MacKenzie TA, Surrey ES, Racowsky C; Society for Assisted Reproductive Technology Writing Group. Optimizing the number of cleavage stage embryos to transfer on day 3 in women 38 years of age and older: a Society for Assisted Reproductive Technology database study. Fertil Steril 2009;91:767-76.

4. Stern JE, Goldman MB, Hatasaka H, MacKenzie TA, Racowsky C, Surrey ES; Society for Assisted Reproductive Technology Writing Group. Optimizing the number of blastocyst stage embryos to transfer on day 5 or 6 in women 38 years of age and older: a Society for Assisted Reproductive Technology database study. Fertil Steril 2009;91:157-66.

Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2011.03.016

The Authors Respond:

We thank Drs. Verit for their interest in our paper (1) and their insightful comments. We agree that many factors would have contributed to the observed increase in IVF effectiveness between the two time periods in our study, especially those they highlighted (refer also to paragraph five in our discussion). However, the main focus of our paper was not on a comparison between the two time periods and we did not base the conclusions of our study on such a comparison. Rather, our main analysis focused on data from the later time period (1993-2002).

We used these data to estimate IVF effectiveness according to the woman’s age at the start of IVF treatment, as shown in Fig 1 (A). We then calculated the cumulative probability of IVF success according to the number of cycles (Fig 2) and, based on the results of these two analyses, combined with the observation that couples undertake, on average, three cycles, we concluded that an increase in the average number of cycles undertaken would likely lead to a further overall increase in IVF effectiveness beyond the improvements already observed.

Drs. Verit make the point that IVF effectiveness could also be estimated based on the many factors other than age at start of treatment, including cause and duration of infertility; we agree with them. It would, however, require a much larger study population to estimate IVF effectiveness within finely stratified subgroups with a reasonable degree of precision.

Louise Maree Stewart, BSc(Hons) GradDipPHa
C. D’Arcy J Holman, M.P.H., Ph.D, F.A.F.P.H.Ma
Roger Hart, M.D., C.R.E.I.b
Judith Finn, Ph.D., R.N.c
Qun Mai, M.B.B.S., M.P.H.a
David B Preen, Ph.D.a

a School of Population Health, The University of Western Australia
b School of Women’s and Infants Health, The University of Western Australia and Fertility Specialists of Western Australia
c Discipline of Emergency Medicine, The University of Western Australia

References
1. Stewart LM, Holman CD, Hart R, Finn J, Mai Q, Preen DB. How effective is in vitro fertilization, and how can it be improved? Fertil Steril 2011; Feb [Epub ahead of print].

Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2011.03.017

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