In Vitro Fertilization the Natural Way
Jacques Kadoch, MD
Table of content
Introduction
History
nIVF: How it works ... and why
Who should try natural IVF?
Contraindications of nIVF
Conclusion
Introduction
There has long been a demand for an IVF technique that works on a woman’s natural cycle, without ovarian stimulation. The answer is natural cycle IVF (nIVF). Increasing numbers of infertile couples are attracted to this alternative protocol, which seems to come closer to the ideal IVF scenario: to conceive an embryo with high implantation potential at the start of a single pregnancy – but with minimal medical intervention.
History
Twenty-five years ago, Edwards and Steptoe achieved the first human pregnancy through IVF after transferring an embryo from a natural cycle. In these early years, doctors had to depend entirely on the cycle’s natural timing. This meant that oocyte retrieval often took place in the middle of the night, under general anesthetic, and required a laparoscopy.1 As there was no medication available at the time to prevent spontaneous premature ovulation, the results from these IVF cycles were quite poor. In order to implant several embryos at once, nature had to be forced. With the advent of ovarian stimulation treatments, natural cycle IVF was abandoned in favour of IVF with ovarian stimulation.
More recently, in France, Professor René Frydman and his team have developed a procedure that can control the risk of premature ovulation and reduce the rejection rate by using gonadotropin-releasing hormone (GnRH) agonists, a new class of drugs now available. The dominant follicle is still selected naturally, but the team then decides the right moment to trigger ovulation so as to increase the cycle’s effective yield.2
nIVF: How it works ... and why
IVF with ovarian stimulation works on strength in numbers: you simply obtain as many follicles, retrieve as many oocytes and then create as many embryos as possible. Ideally, having multiple embryos should make it possible to choose the best one, according to well-established morphological criteria. A strict policy of single embryo transfer, adopted by some European countries, has not yet gained widespread acceptance in North America. Instead, we see an unsettling trend toward transferring multiple embryos, a practice that is often defended in the name of securing maximum success for couples who must endure a lengthy, rigorous and costly treatment. Stiff competition among certain fertility clinics, however, is also a factor. Good medical practice cautions that the percentage of multiple pregnancies should not exceed 30% of all clinical pregnancies achieved, but unfortunately, this number is often exceeded. In natural cycle IVF, the risk of multiple pregnancies is reduced to monozygote pregnancies (identical twins). What’s more, not having an excess number of embryos can be perceived as a major advantage for couples who hope to avoid having to choose between freezing or destroying these unused embryos.
nIVF has several other advantages. The procedures involved are relatively simple compared to the various ovarian stimulation protocols. Even when monitoring is identical (and it’s becoming increasingly similar, in certain instances) minimal drugs are used due to an absence of desensitization and ovarian stimulation. This absence of stimulation also eliminates the risk of ovarian hyperstimulation syndrome (OHSS). Last but not least, it’s possible to perform nIVF in consecutive cycles.
Who should try natural IVF?
The decision to develop a natural cycle IVF program at the OVO Fertility Clinic was not made for philosophical reasons, but because we knew it might appeal to certain infertile couples.
nIVF is an attractive alternative for certain types of patients who have an unfavourable prognosis. It may be an option in cases of implantation failure – the absence of pregnancy despite transfer of several high-quality embryos from a stimulated cycle. (In fact, ovarian stimulation leads to a significant increase in estradiol levels, which can be harmful to embryonic implantation.)3 Young patients with an abnormally low follicular ovarian reserve are also good candidates; it’s probably better to obtain one embryo from a natural cycle, rather than a smaller-than-normal number of embryos after a maximum-dose stimulation. What makes it even more attractive is that implantation rates (the chance of embryo implantation after transfer to the uterus) through nIVF are higher than those attained after stimulation.4
Of course, nIVF can also be offered to couples with a good prognosis. In fact, many couples have considered the benefits of this treatment after a failed vasovasostomy. nIVF is then performed along side the microinjection of a spermatozoid (ICSI) obtained through epididymal aspiration. This often involves a situation where the man already has children, but wants his spouse, who is often young and has no fertility problems, to avoid ovarian stimulation, which could lead to a twin pregnancy.5
nIVF is also a viable alternative for women with a previous history of hormone-dependent cancer, and who would like to avoid ovarian stimulation
Contraindications of nIVF
Natural cycle IVF has its detractors, who maintain an ongoing lookout for evidence of premature ovulation, increased rejection rates, the need for IVF teams to be available around the clock, higher puncture rates without oocyte collection and, last but not least, low pregnancy rates.
nIVF is not for everybody, and IVF with ovarian stimulation is still the most appropriate treatment in some cases, especially for patients age 38 and older.
Furthermore, monitoring the natural cycle is so subtle and precise that expertise in this area cannot be rapidly acquired.
Conclusion
To sum up, it seems clear that natural cycle IVF can be a sound alternative, among others, for couples suffering from unexplained infertility, tubal factor or male factor infertility; for patients who have suffered repeated implantation failure using IVF with ovarian stimulation; and for young patients who lack sufficient ovarian reserves for IVF with ovarian stimulation.
Practically all IVF in Canada today is achieved after ovarian stimulation. But from now on, natural cycle IVF will be part of the contemporary therapeutic repertoire of infertility treatment.
Dr. Jacques Kadoch completed his medical studies in the Faculty of Medicine Saint-Antoine (Pierre and Marie Curie University, Paris VI), before preparing for the concours de l’Internat, which he received in 1995. After specializing in obstetrics and gynecology in Paris for five years, he became Clinical Director under Professor René Frydman, an internationally renowned pioneer in the field of contemporary infertility treatment. He further developed his strong theoretical and practical training with a fellowship in the Endocrinology of Reproduction and Infertility at the University of Montreal, where he is now Associate Clinical Professor in the department of Obstetrics and Gynecology. He is also a consultant at the OVO Fertilitiy Clinic in Montreal. With numerous scientific publications to his credit, he is in a number of research projects, and is particularly interested in developing new techniques such as natural cycle in vitro fertilization and in vitro maturation.
[NOTES]
1. Edwards, R. G., Steptoe, P. C. and Purdy, J. M. (September1980). Establishing full-term human pregnancies using cleaving embryos grown in vitro. British Journal of Obstetrics and Gynaecology 87(9), pp. 737–56.
2. Rongieres-Bertrand, C., Olivennes, F., Righini, C., Fanchin, R., Taieb J., Hamamah, S., Bouchard, P. and Frydman, R. (March 1999). Revival of the natural cycles in in vitro fertilization with the use of a new gonadotrophin-releasing hormone antagonist (Cetrorelix): A pilot study with minimal stimulation. Human Reproduction 14 (3), pp. 683–88.
3. Lédée-Bataille, N., Dubanchet, S., Kadoch, I. J., Castelo-Branco, A., Frydman, R. and Chaouat, G. (July 2004). Controlled natural in vitro fertilization may be an alternative for patients with repeated unexplained implantation failure and a high uterine natural killer cell count. Fertility & Sterility 82 (1), pp. 234–36
4. Castelo-Branco, A., Frydman, N., Kadoch, I. J., Le Du, A., Fernandez, H., Fanchin, R, and Frydman, R. (October 2004). The role of the semi-natural cycle as a treatment option for patients with a poor prognosis for successful in vitro fertilization. Journal de gynécologie, obstétrique et biologie de la reproduction (Paris) 33 (6, Part 1), pp. 518–24.
5. Kadoch, I. J., Phillips, S.J., Hemmings, R., Lapensée, L., Couturier, B. and Bissonnette, F. Ongoing pregnancy after ICSI of frozen-thawed percutaneous epididymal sperm aspiration (PESA) retrieved spermatozoa and in vitro fertilization in a natural cycle (nIVF). RBMonline. 2005. 10(5), pp.650-652
