Clare Boothroyd

Consensus statement on prevention and detection of ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome is an important condition with considerable morbidity and a small risk of mortality, which most commonly results as an iatrogenic condition following follicular stimulation of the ovaries.

Acupuncture to improve live birth rates for women undergoing in vitro fertilization: a protocol for a randomized controlled trial

BackgroundIVF is a costly treatment option for women, their partners, and the public. Therefore new therapies that improve reproductive and health outcomes are highly desirable. There is a growing body of research evaluating the effect of acupuncture administered during IVF, and specifically on the day of embryo transfer (ET). Many trials are heterogeneous and results inconsistent. There remains insufficient evidence to determine if acupuncture can enhance live birth rates when used as an adjunct to IVF treatment.The study will determine the clinical effectiveness of acupuncture with improving the proportion of women undergoing IVF having live births. Other objectives include: determination of the cost effectiveness of IVF with acupuncture; and examination of the personal and social context of acupuncture in IVF patients, and examining the reasons why the acupuncture may or may not have worked.MethodsWe will conduct a randomized controlled trial of acupuncture compared to placebo acupuncture.Inclusion criteria include: women aged less than 43 years; undergoing a fresh IVF or ICSI cycle; and restricted to women with the potential for a lower live birth rate defined as two or more previous unsuccessful ETs; and unsuccessful clinical pregnancies of quality embryos deemed by the embryologist to have been suitable for freezing by standard criteria. Women will be randomized to acupuncture or placebo acupuncture. Treatment is administered on days 6 to 8 of the stimulated cycle and two treatments on the day of ET. A non-randomized cohort of women not using acupuncture will be recruited to the study. The primary study outcome is the proportion of women reporting a live birth. Secondary outcomes include the proportion of women reporting a clinical pregnancy miscarriage prior to 12 weeks, quality of life, and self-efficacy. The sample size of the study is 1,168 women, with the aim of detecting a 7% difference in live births between groups (P = 0.05, 80% power).DiscussionThere remains a need for further research to add significant new knowledge to defining the exact role of certain acupuncture protocols in the management of infertility requiring IVF from a clinical and cost-effectiveness perspective.Clinical Trial RegistrationAustralian and New Zealand Clinical Trial Registry ACTRN12611000226909

RANZCOG CREI Consensus Statement on treatment of Ovarian Hyperstimulation Syndrome

Ovarian hyperstimulation syndrome (OHSS) is an uncommon but important iatrogenic condition associated with considerable morbidity and a small risk of mortality.

Assisted reproductive technology in Australia and New Zealand: cumulative live birth rates as measures of success

Objectives: To estimate cumulative live birth rates (CLBRs) following repeated assisted reproductive technology (ART) ovarian stimulation cycles, including all fresh and frozen/thaw embryo transfers (complete cycles).

Twinning: Double, double, toil and trouble?

Australia and New Zealand (ANZ) have led the world in the reduction of twinning following the use of assisted reproduction technologies (ART) which in 2013 was 5.6% of all ART pregnancies This compares with 16.6% in UK and 26.1% in USA for the same period. The increased dizygotic twinning observed globally since 1970 has been attributed to fertility treatments (ovulation induction and ART) but the striking feature of Newitt et al.’s Figure 1 is the relatively small proportion of twins attributable to ART despite a rapid rise in the number of pregnancies following ART. If all single embryo transfers (SET) were actually double embryo transfers (DET) the number of twins was estimated to be 1000 per 100 000 or half of all twins in ANZ. The adoption of SET in ANZ has occurred without mandate or regulation and has been driven by clinicians, often practising obstetricians, working in an environment where funding of ART is supported by government. Most dizygotic twinning in ANZ is not related to ART. Dizygotic (DZ) twinning is a marker of fecundity of a population and is influenced by increased maternal age, nutrition, genetic constitution and other factors. It is these influences – particularly deferral of childbearing and improved nutrition – which have probably provided the major contribution to the rise in DZ twinning seen globally since 1970. The contribution of ovulation induction agents such as clomiphene and low-dose follicle stimulating hormone (FSH) which have twin pregnancy rates of 6–14% and up to 25% depending on expertise, is uncertain. Alternatives to clomiphene, such as letrozole (not yet approved for use as an ovulation induction agent by the Therapeutic Goods Administration in Australia, but available in New Zealand) and ovarian drilling, have greatly reduced risk of twins compared to clomiphene and FSH. Monozygotic twinning has not increased significantly over time and is perhaps only marginally increased by ART, estimated to occur in 1–2% of all ART pregnancies. Miller et al. provoke debate by the proposal to convert what has been a successful voluntary collective action to a mandatory process. This proposal has merit – women aged over 40 with a reduced chance of achieving a pregnancy from ART are particularly likely to express desire for DET. These women are more likely to have medical problems (e.g. hypertension and insulin resistance) and to have uterine problems (e.g. fibroids and adenomyosis) which increase the maternal risk of pregnancy and predispose to preterm birth. It is older women using their own oocytes who are at risk of twin pregnancy with discordant fetal aneuploidy/euploidy and its consequent complexities and ethical dilemmas. Commissioning couples of surrogate (gestational carriage) arrangements frequently express a wish for twin pregnancy to provide a complete family from one cryopreserved embryo transfer cycle (and the costs of surrogate arrangements are considerable) but in doing so increase the risk to the women undertaking an altruistic but not risk-free life event. Mandating SET in such settings (older women and surrogate arrangements) seems wise but will not be universally effective as 2.3% of pregnancies following SET are twin pregnancies with only one in five twin pregnancies being estimated as due to concomitant natural conception (and therefore preventable); the rest are presumed to be monozygotic twins. As women age the risk of an adverse event during their pregnancy becomes higher. Is a twin pregnancy at 40 safer than a singleton pregnancy at 40 and a subsequent singleton pregnancy at 43 or perhaps 45 years of age? While the costs of parenting twins are more than double the cost of raising two singletons there are economies from reduced time out of the workforce in order to parent. However, few couples undertaking ART and requesting DET are aware that twinning is associated with increased maternal morbidity. Once twins have survived the first few years of life (and ART twins are just as likely as spontaneously conceived twins to do so) their life expectancy is not reduced compared to singletons. Twins have lower risk of suicide. One in 30 adults in the USA has a twin sibling and as such, community experience of twins is positive and twins are seen as special. However, the loss of twins (and the sevenfold increase in mortality seen in low and medium resource settings) is to the wider community largely unseen and this results in cognitive dissonance between the medical profession and healthcare consumers. The potential for ART to contribute to twinning, which is seen in other countries, is significantly influenced by public funding of ART and increasing out-of-pocket costs. Reduction of funding of ART will increase pressure on providers of ART and their patients to perform DET and thereby increase multiple births and all of their attendant costs. Mandating SET might at first seem to solve this problem. However, mandates in clinical care create tension between expressed needs for patient autonomy and collective utilitarianism and resource allocation. Restrictions of access to services cause people to look elsewhere for what they cannot have, as the rise of crossborder reproductive care has shown. A key driver to cross-border care is law evasion and of this we must be mindful. The imperative becomes maintenance of funding for ART and perhaps, as proposed by Miller et al., financial incentives to encourage SET.