The use of oil-soluble contrast media for tubal flushing in infertility: A consensus statement from ACCEPT (Australasian CREI Consensus Expert Panel on Trial evidence).

Good evidence that oil-soluble contrast media (OSCM) enhances pregnancy rates when used to assess fallopian tube patency by hysterosalpingogram has prompted rapid clinical uptake by some fertility doctors and imaging specialists in Australia and New Zealand. The ACCEPT group met in July 2019 to develop a consensus document outlining the indications for and safe use of OSCM, to inform and guide clinicians interested in offering procedures using this media to couples with infertility.

ANZSREI consensus statement on elective oocyte cryopreservation.

BACKGROUND: One in six Australian women and couples suffer infertility. A rising proportion relates to advanced maternal age, associated with poorer oocyte quality and in vitro fertilisation (IVF) outcomes. Internationally, oocyte cryopreservation technology applied to oocytes vitrified before 35 years provides similar live-birth statistics compared to IVF treatment using fresh oocytes. Oocyte cryopreservation is accessible in Australasian settings and elective uptake is increasing. For women accessing treatment, oocyte cryopreservation may expand future family building options. AIMS: To develop the first Australasian Certification in Reproductive Endocrinology and Infertility (CREI) subspecialist-led consensus guideline on oocyte cryopreservation. METHODS: The ANZSREI ACCEPT (Australasian CREI Consensus Expert Panel on Trial evidence group) met in 2017 and 2018 and identified clinical aspects of care for inclusion and review. Review of the available evidence was conducted and consensus statements prepared. Areas of dissent of expert opinion and for further research were noted. RESULTS: Consensus was reached on definition and best practice in oocyte cryopreservation for freeze method, controlled ovarian stimulation, medical risk reduction and treatment and outcomes counselling. The term 'social egg freezing' may marginalise, stigmatise or attribute social blame to women, and there is a need to revise this to a neutral and non-judgemental term such as elective or planned oocyte cryopreservation. CONCLUSION: Oocyte cryopreservation has the potential to improve cumulative live birth outcomes for women. Implementation of this guideline should facilitate an optimal approach for providing care.

Effect of Acupuncture vs Sham Acupuncture on Live Births Among Women Undergoing In Vitro Fertilization: A Randomized Clinical Trial.

Importance: Acupuncture is widely used by women undergoing in vitro fertilization (IVF), although the evidence for efficacy is conflicting. Objective: To determine the efficacy of acupuncture compared with a sham acupuncture control performed during IVF on live births. Design, Setting, and Participants: A single-blind, parallel-group randomized clinical trial including 848 women undergoing a fresh IVF cycle was conducted at 16 IVF centers in Australia and New Zealand between June 29, 2011, and October 23, 2015, with 10 months of pregnancy follow-up until August 2016. Interventions: Women received either acupuncture (n = 424) or a sham acupuncture control (n = 424). The first treatment was administered between days 6 to 8 of follicle stimulation, and 2 treatments were administered prior to and following embryo transfer. The sham control used a noninvasive needle placed away from the true acupuncture points. Main Outcomes and Measures: The primary outcome was live birth, defined as the delivery of 1 or more living infants at greater than 20 weeks' gestation or birth weight of at least 400 g. Results: Among 848 randomized women, 24 withdrew consent, 824 were included in the study (mean [SD] age, 35.4 [4.3] years); 371 [45.0%] had undergone more than 2 previous IVF cycles), 607 proceeded to an embryo transfer, and 809 (98.2%) had data available on live birth outcomes. Live births occurred among 74 of 405 women (18.3%) receiving acupuncture compared with 72 of 404 women (17.8%) receiving sham control (risk difference, 0.5% [95% CI, -4.9% to 5.8%]; relative risk, 1.02 [95% CI, 0.76 to 1.38]). Conclusions and Relevance: Among women undergoing IVF, administration of acupuncture vs sham acupuncture at the time of ovarian stimulation and embryo transfer resulted in no significant difference in live birth rates. These findings do not support the use of acupuncture to improve the rate of live births among women undergoing IVF. Trial Registration: anzctr.org.au Identifier: ACTRN12611000226909.

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). DESIGN, SETTING AND PARTICIPANTS: Prospective follow-up of 56 652 women commencing ART in Australian and New Zealand during 2009-2012, and followed until 2014 or the first treatment-dependent live birth. MAIN OUTCOME MEASURES: CLBRs and cycle-specific live birth rates were calculated for up to eight cycles, stratified by the age of the women (< 30, 30-34, 35-39, 40-44, > 44 years). Conservative CLBRs assumed that women discontinuing treatment had no chance of achieving a live birth if had they continued treatment; optimal CLBRs assumed that they would have had the same chance as women who continued treatment. RESULTS: The overall CLBR was 32.7% (95% CI, 32.2-33.1%) in the first cycle, rising by the eighth cycle to 54.3% (95% CI, 53.9-54.7%) (conservative) and 77.2% (95% CI, 76.5-77.9%) (optimal). The CLBR decreased with age and number of complete cycles. For women who commenced ART treatment before 30 years of age, the CLBR for the first complete cycle was 43.7% (95% CI, 42.6-44.7%), rising to 69.2% (95% CI, 68.2-70.1%) (conservative) and 92.8% (95% CI, 91.6-94.0) (optimal) for the seventh cycle. For women aged 40-44 years, the CLBR was 10.7% (95% CI, 10.1-11.3%) for the first complete cycle, rising to 21.0% (95% CI, 20.2-21.8%) (conservative) and 37.9% (95% CI, 35.9-39.9%) (optimal) for the eighth cycle. CONCLUSION: CLBRs based on complete cycles are meaningful estimates of ART success, reflecting contemporary clinical practice and encouraging safe practice. These estimates can be used when counselling patients and to inform public policy on ART treatment.

RANZCOG CREI Consensus Statement on treatment of Ovarian Hyperstimulation Syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is an uncommon but important iatrogenic condition associated with considerable morbidity and a small risk of mortality. This document gathers the consensus of a group of fertility subspecialists to aid health professionals in the development of protocols and guidelines for the management of women with OHSS. AIM: To produce evidence-based consensus statements on the treatment of ovarian hyperstimulation syndrome (OHSS). METHODS: The CREI Consensus Group met in 2013 and 2014 and identified issues for inclusion and review. Review of the available evidence was conducted and consensus statements prepared. Areas of dissent of expert opinion and for further research were noted. RESULTS: There is a paucity of good data regarding the treatment of this condition, and much of the treatment is supportive in nature. Most of the management recommendations are based on good clinical practice points, rather than evidence from randomised trials. CONCLUSION: OHSS is an uncommon but serious condition for which there are a number of proven preventative strategies. Once OHSS is present, the treatment of OHSS is mainly supportive, and more research is required to elucidate treatment options targeted specifically at the main causative factors, to better treat the condition.

Consensus statement on prevention and detection of ovarian hyperstimulation syndrome.

BACKGROUND: 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. AIM: To produce evidence-based and consensus statements on the prevention and detection of ovarian hyperstimulation syndrome (OHSS). METHOD: The CREI Consensus Group met in 2008 and identified issues for inclusion and review. Review of the available evidence was conducted and consensus statements prepared. Areas of dissent of expert opinion and for further research were noted. RESULTS: The group considered that there is a need for standardisation of the definition and classification of the clinical syndrome of OHSS to allow further conclusive research. Interventions with evidence of effect in reducing OHSS include the use of metformin in women with PCOS, use of GnRH antagonist rather than GnRH agonist and use of GnRH agonist triggers in GnRH antagonist stimulation cycles. The consensus view was that reducing the dose of FSH, freezing all embryos and transferring a single embryo were appropriate interventions to reduce OHSS. Agreement could not be reached on coasting, the lowest number of oocytes to consider freezing all embryos and management after cancellation of oocyte collection. CONCLUSION: OHSS is a serious condition for which there are a number of proven preventative strategies. OHSS is an area requiring ongoing research and development of a universally agreed definition will allow development of optimal prevention strategies and facilitate improved early detection of women at risk.

The effects of vaginal lubricants on sperm function: an in vitro analysis.

BACKGROUND: Despite being marketed as "sperm friendly", some vaginal lubricants are known to be detrimental to sperm function and therefore could negatively affect fertility. Many others have not yet been assessed in regards to their effect on sperm function. This issue may concern couples trying to conceive both naturally and via artificial reproductive technologies (ART). AIM: The aim of this research was to analyse the effects that lubricants, commonly used in the setting of natural conception and ART, have on sperm function in an in vitro setting. This was done by assessing sperm motility, vitality and DNA fragmentation following treatment with commercial lubricants or control preparations. We have attempted to mimic the conditions of the vaginal environment in our clinical trial, and so have compiled a list of lubricants that are likely to have minimal negative effect on sperm function in vivo or are "sperm friendly". METHODS: Ten samples were obtained for the study from patients attending a fertility clinic. Once collected, the sperm samples were prepared by density gradient centrifugation and incubated with 11 different lubricants including positive and negative controls for 30 min at 37 °C to mimic the temperature inside the female reproductive tract. Sperm motility, vitality and DNA fragmentation were assessed to determine the effects of the lubricants on sperm function and DNA integrity. RESULTS: Nine lubricants were investigated including Sylk™, Conceive Plus®, glycerol, Johnson's® Baby Oil, SAGE® Culture Oil, Yes®, Forelife™, MaybeBaby® and Pre-seed®. The lubricant which had the best results in terms of vitality, at 92%, was Pre-seed® and the worst was Forelife™ with 28% vitality. In terms of motility, Pre-seed® resulted in the highest percentage of spermatozoa with progressive motility at 86% and Sylk™ resulted in the lowest percentage of progressively motile cells in the sample with 31% of sperm progressively motile. There were no significant effects on DNA integrity. CONCLUSIONS: Pre-seed® was the lubricant which had the least negative effect on sperm function, with Conceive Plus® a close second, due to the significantly higher sperm motility and vitality parameters measured following lubricant exposure.

Clomiphene and anti-oestrogens for ovulation induction in PCOS.

BACKGROUND: Subfertility due to anovulation is a common problem in women. First-line oral treatment is with anti-oestrogens, for example clomiphene citrate, but resistance (failure to ovulate) may be apparent with clomiphene. Alternative and adjunctive treatments have been developed such as tamoxifen, dexamethasone, and bromocriptine. OBJECTIVES: To determine the relative effectiveness of anti-oestrogen agents alone or in combination with other medical therapies in women with subfertility associated with anovulation, possibly caused by polycystic ovarian syndrome (PCOS). SEARCH STRATEGY: A search was conducted using the Cochrane Menstrual Disorders and Subfertility Group Trials Register (May 2009), CENTRAL (The Cochrane Library 2009, Issue 2), MEDLINE (1966 to May 2009), and EMBASE (1980 to May 2009) for identification of relevant randomised controlled trials (RCTs). The United Kingdom National Institute for Clinical Excellence (NICE) guidelines and the references of relevant reviews and RCTs were searched. SELECTION CRITERIA: RCTs comparing oral anti-oestrogen agents for ovulation induction (alone or in conjunction with medical therapies) in anovulatory subfertility were considered. Insulin sensitising agents, aromatase inhibitors, and hyperprolactinaemic infertility were excluded. DATA COLLECTION AND ANALYSIS: Data extraction and quality assessment were done independently by two review authors. The primary outcome was live birth; secondary outcomes were pregnancy, ovulation, miscarriage, multiple pregnancy, overstimulation, ovarian hyperstimulation syndrome, and women reported adverse effects. MAIN RESULTS: This is a substantive update of a previous review. Fifteen RCTs were included. One trial reported live birth. Miscarriage, multiple pregnancy rates and adverse events were poorly reported.Clomiphene was effective in increasing pregnancy rate compared to placebo (OR 5.8, 95% CI 1.6 to 21.5) as was clomiphene plus dexamethasone treatment (OR 9.46, 95% CI 5.1 to 17.7) compared to clomiphene alone. No evidence of a difference in effect was found between clomiphene versus tamoxifen or clomiphene in conjunction with human chorionic gonadotrophin (hCG) versus clomiphene alone.The remaining results had only one study in each comparison. A significant improvement in the pregnancy rate was reported for clomiphene plus combined oral contraceptives versus clomiphene alone. No evidence of a difference in effect on pregnancy rate was found with any of the other comparisons. AUTHORS' CONCLUSIONS: This review shows evidence supporting the effectiveness of clomiphene citrate and clomiphene in combination with dexamethasone for pregnancy rate only. There is limited evidence on the effects of these drugs on outcomes such as miscarriage. Evidence in favour of these interventions is flawed due to the lack of evidence on live births.

Normal live births after intracytoplasmic sperm injection in a man with the rare condition of Eagle-Barrett syndrome (prune-belly syndrome).

OBJECTIVE: To report the first live births of male infants resulting from intracytoplasmic sperm injection (ICSI) using spermatozoa from a man with Eagle-Barrett syndrome (EBS). DESIGN: Case report. SETTING: Assisted conception unit within a private hospital. PATIENT(S): An infertile couple. INTERVENTIONS: An infertile couple received repeated treatment with ICSI. MAIN OUTCOME MEASURE(S): Clinical pregnancy and a normal live birth. RESULT(S): In 2008, after microinjection of ten oocytes, the transfer of a single expanded blastocyst led to the premature birth of a morphologically normal male infant at 18 weeks' gestation. This outcome followed preterm rupture of membranes and possible cervical incompetence. In 2009, after microinjection of six oocytes, transfer of a single 5-cell embryo led to a singleton pregnancy, with emergency cervical cerclage being performed at 21 weeks. A healthy male infant was born at 30 weeks, with no evidence of EBS, by lower-segment cesarean section for breech presentation and premature labor. In 2012, after elective laparoscopic placement of cervical suture, microinjection of ten oocytes and transfer of a single 4-cell embryo led to a singleton pregnancy with a healthy male infant, with no evidence of EBS, being born by cesarean section at 38 weeks. CONCLUSION(S): This report suggests that EBS is not transmitted to male offspring via ICSI.

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

BACKGROUND: IVF 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. METHODS: We 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). DISCUSSION: There 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 REGISTRATION: Australian and New Zealand Clinical Trial Registry ACTRN12611000226909.

Higher-order multiple pregnancy associated with metformin in women with polycystic ovary syndrome: two cases and review of the literature.

OBJECTIVE: To describe the first reported cases of two women with polycystic ovary syndrome (PCOS) desirous of pregnancy who conceived trichorionic pregnancies following ovulation induction with metformin alone and metformin plus clomiphene. DESIGN: Case report. SETTING: Private fertility practice. PATIENT(S): Two women with polycystic ovary syndrome, one lean and one overweight, both oligoovulatory and not undertaking their first cycle of treatment. INTERVENTION(S): Ovulation induction by metformin alone or in combination with clomiphene MAIN OUTCOME MEASURE(S): Higher-order multiple pregnancy (triplet or greater). RESULT(S): Two cases of trichorionic pregnancy. CONCLUSION(S): This is the first report of higher-order multiple pregnancies resulting from the use of either metformin alone or in combination with clomiphene. The additive effects of adjunctive treatments such as weight reduction, ovarian drilling, and clomiphene and metformin therapy may result in an increased incidence of higher-order multiple pregnancy and women need to be counseled about this risk. Further research is required to quantify the risk of this event per treatment cycle.