Elsevier

The Lancet

Volume 365, Issue 9473, 21–27 May 2005, Pages 1807-1816
The Lancet

Review
Multiple birth resulting from ovarian stimulation for subfertility treatment

https://doi.org/10.1016/S0140-6736(05)66478-1Get rights and content

Summary

Assisted reproductive technologies (ARTs) aim to increase a woman's chances of becoming pregnant by bringing many female and male gametes into close proximity. Techniques to achieve this objective include ovarian hyperstimulation by maturation of several oocytes, intrauterine insemination (IUI) of concentrated sperm, or in-vitro fertilisation (IVF) by bringing gametes together outside the female body. The very nature of ovarian hyperstimulation—with or without IUI—enhances the risk of multiple pregnancy (eg, two or more babies). In most IVF cycles, more than one embryo is transferred, again resulting in an increased chance of multiple pregnancy. Developed societies have witnessed a large rise in prevalence of twin, triplet, and higher order multiple births, mainly resulting from ARTs. The primary aim of this Review is to increase awareness of the many implications of the present iatrogenic epidemic of multiple births. The background of ovarian hyperstimulation, trends supporting current practice, and strategies to reduce the chance of multiple pregnancy are highlighted.

Published online February 4, 2005 http://image.thelancet.com/extras/04art6002web.pdf

Section snippets

Physiology of follicle development

At birth, the ovaries contain around 2 million primordial follicles in a state of meiotic arrest. This follicle stock is subsequently depleted over many decades, until final exhaustion coinciding with menopause marks the end of the reproductive lifespan. Follicle depletion happens by growth initiation of resting follicles, a process—referred to as primary or continuous recruitment—that is independent of gonadotropins.25 With the demise of the corpus luteum coinciding with diminished steroid

Ovarian hyperstimulation strategies

Drugs for stimulation of ovarian function either raise endogenous pituitary FSH output by interfering with negative oestrogen feedback, using antioestrogens such as clomifene citrate, or supplement FSH directly. Other compounds that affect oestrogen feedback, such as aromatase inhibitors, are under investigation for ovarian stimulation. Depending on the treatment aim and the individual ovarian response of the patient, exogenous human menopausal gonadotropin (obtained from urine of

Clinical implications of ovarian hyperstimulation

Ovarian hyperstimulation is sometimes combined with IUI as an empirical treatment in patients with unexplained subfertility, although the clinical value of this approach is much debated. Since national registries of these interventions do not exist, we do not know how many hyperstimulation cycles are done every year, the overall conception and multiple pregnancy rates, or geographic variations in clinical practice.

Guzick and colleagues48 did a retrospective analysis of 45 published reports and

In-vitro fertilisation

IVF is one of the most comprehensively registered interventions in clinical medicine. In a US report from 2001 on 80 864 IVF cycles, the rate of oocyte retrieval was 86%, embryo transfer 81%, pregnancy 33%, and livebirths 27%, per started cycle.58 Although a proportion of cycles fail at every step of the IVF procedure, by far the greatest loss is from failed embryo implantation. The primary cause of such failure is generally thought to be abnormal embryos, although the endometrial factor cannot

Multiple pregnancies

The developed world has witnessed a staggering increase in prevalence of multiple births since the introduction of IVF along with large-scale use of ovarian hyperstimulation. In the USA, twin birth rates rose by 75% between 1980 and 2000, representing around 3% of total births (figure 7).36, 80 Similar trends have been reported for European countries.81 Although an association between high female age and multiple gestation is clear, the delay in childbearing accounts for no more than 30% of the

Strategies to reduce frequency of multiple birth after ART

Awareness is growing that the ever-increasing contribution of ART to multiple births in the developed world is no longer acceptable. The perinatal morbidity and mortality directly related to multiple births (panel 1) overwhelm any argument in favour of more rapid family building by means of multiple births. Yet, both patients98, 99, 100 and infertility doctors101 remain insufficiently aware of medical complications and parent stress associated with multiple births. Hence, any strategy to reduce

Search strategy and selection criteria

A MEDLINE search was done with the following keywords: fetal outcome, multiple pregnancies, infertility, therapy, IVF, and IUI. We focused on recent papers (within 3 years), but highly regarded reports from before this time were not excluded. We subsequently searched the reference list of articles identified by our search strategy and selected further reports we judged relevant. Several review papers or book chapters were included, covering areas beyond the scope of the current review.

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