Medicine in the marketplace: clinician and patient views on commercial influences on assisted reproductive technology.

RESEARCH QUESTION: What are the views and experiences of patient and expert stakeholders on the positive and negative impacts of commercial influences on the provision of assisted reproductive technology (ART) services, and what are their suggestions for governance reforms? DESIGN: Semi-structured interviews were conducted with 31 ART industry experts from across Australia and New Zealand and 25 patients undergoing ART from metropolitan and regional Australia, between September 2020 and September 2021. Data were analysed using thematic analysis. RESULTS: Expert and patient participants considered that commercial forces influence the provision of ART in a number of positive ways - increasing sustainability, ensuring consistency in standards and providing patients with greater choice. Participants also considered commercial forces to have a number of negative impacts, including increased costs to government and patients; the excessive use of interventions that lack sufficient evidence to be considered part of standard care; inadequately informed consent (particularly with regard to financial information); and threats to patient-provider relationships and patient-centred care. Participants varied in whether they believed that professional self-regulation is sufficient. While recognizing the benefits of commercial investment in healthcare, many considered that regulatory reforms, as well as organizational cultural initiatives, are needed as means to ensure the primacy of patient well-being. CONCLUSIONS: The views expressed in this study should be systematically and critically examined to derive insights into how best to govern ART. These insights may also inform the design and delivery of other types of healthcare that are provided in the private sector.

IgG exacerbates genital chlamydial pathology in females by enhancing pathogenic CD8+ T cell responses.

Chlamydia trachomatis infections are an important sexually transmitted infection that can lead to inflammation, scarring and hydrosalpinx/infertility. However, infections are commonly clinically asymptomatic and do not receive treatment. The underlying cause of asymptomatic immunopathology remains unknown. Here, we demonstrate that IgG produced during male infection enhanced the incidence of immunopathology and infertility in females. Human endocervical cells expressing the neonatal Fc Receptor (FcRn) increased translocation of human IgG-opsonized C. trachomatis. Using total IgG purified from infected male mice, we opsonized C. muridarum and then infected female mice, mimicking sexual transmission. Following infection, IgG-opsonized Chlamydia was found to transcytose the epithelial barrier in the uterus, where it was phagocytosed by antigen-presenting cells (APCs) and trafficked to the draining lymph nodes. APCs then expanded both CD4+ and CD8+ T cell populations and caused significantly more infertility in female mice infected with non-opsonized Chlamydia. Enhanced phagocytosis of IgG-opsonized Chlamydia significantly increased pro-inflammatory signalling and T cell proliferation. As IgG is transcytosed by FcRn, we utilized FcRn-/- mice and observed that shedding kinetics of Chlamydia were only affected in FcRn-/- mice infected with IgG-opsonized Chlamydia. Depletion of CD8+ T cells in FcRn-/- mice lead to a significant reduction in the incidence of infertility. Taken together, these data demonstrate that IgG seroconversion during male infection can amplify female immunopathology, dependent on FcRn transcytosis, APC differentiation and enhanced CD8 T cell responses.

Non-invasive tests for endometriosis are here; how reliable are they, and what should we do with the results?

A reliable non-invasive biomarker for endometriosis is highly likely in the coming years. In the lead-up to this, clinicians need to be aware of commercially available tests as they become accessible, be aware of the level of evidence to support them and be prepared to counsel and manage patients who present with the results of such tests. One such test gaining popularity in Europe was developed using a machine-based learning algorithm to analyse thousands of microRNAs based on a 200-patient cohort with suspected endometriosis in France. We explore the background science for this commercially available test; outline the questions that remain to be answered; and caution against its use outside of a research setting.

Antibiotics prior to or at the time of embryo transfer in ART.

BACKGROUND: After an assisted reproductive technology (ART) cycle, embryo transfer (ET) involves the placement of one or more embryos into the uterine cavity, usually by passing a catheter through the cervical os. Despite the transfer of high-quality embryos, many ETs do not result in a pregnancy. There are many factors that may affect the success of ET. There is some evidence to suggest that increased endocervical microbial colonization at the time of ET results in lower pregnancy rates. The association between the cervico-vaginal microbiome and reduced pregnancy rates after ET may indicate either pre-existing dysbiosis in this patient population, or that the passage of the ET catheter itself may be introducing microbes that alter the microbiome of the endometrial cavity or lead to infection. Such an upper genital tract infection, contamination or alteration may have a negative impact on implantation and in vitro fertilization (IVF) success rates by both endometrial and embryonic mechanisms. The administration of antibiotics at the time of ET has been suggested as an intervention to reduce levels of microbial colonization and hence improve pregnancy rates. OBJECTIVES: To evaluate the benefits and harms of antibiotic administration prior to or at the time of embryo transfer (ET) during assisted reproductive technology (ART) cycles. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL (now containing output from two trial registers and CINAHL), MEDLINE, Embase and PsycINFO, together with reference checking and contact with study authors and experts in the field to identify additional studies. The search date was November 2022. SELECTION CRITERIA: We included two randomized controlled trials (RCT) that compared antibiotics administered by any route versus no antibiotics prior to ET. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane, including assessing risk of bias of the included studies using the RoB 2 tool. The primary review outcome was live birth rate (LBR) or ongoing pregnancy, and secondary outcomes were clinical pregnancy rate (CPR), genital tract colonization rate, miscarriage rate, ectopic pregnancy rate, multiple pregnancy rate, fetal abnormalities, adverse events and pelvic infection. MAIN RESULTS: We included two RCTs with 377 women in the review. Using the GRADE method, we assessed the certainty of the evidence as very low to low across measured outcomes. We are uncertain whether antibiotics given prior to or at the time of ET improved LBR (odds ratio (OR) 0.48, 95% confidence interval (CI) 0.10 to 2.23; 1 study, 27 women; low-certainty evidence). The evidence suggests that if LBR without antibiotics was 60%, the rate with antibiotics would be between 13% and 77%. We are uncertain whether antibiotics given prior to or at the time of ET improve CPR (OR 1.01, 95% CI 0.67 to 1.55; I² = 0%; 2 studies, 377 women; low-certainty evidence). If the CPR without antibiotics was 37%, the rate with antibiotics would be between 29% and 48%. The administration of antibiotics prior to or at the time of ET may reduce genital tract colonization slightly (OR 0.59, 95% CI 0.37 to 0.95; 1 study, 130 women; very low-certainty evidence). If the genital tract colonization rate without antibiotics was 29%, the rate with antibiotics would be between 13% and 28%. However, this did not correspond to an effect on the pregnancy outcome. Only one study with low numbers of women reported on miscarriage rate, with one miscarriage reported in the group not receiving antibiotics (OR 4.04, 0.15 to 108.57; 1 study, 27 women; low-certainty evidence). There was insufficient evidence to reach a conclusion regarding adverse effects and other outcomes as no studies reported data suitable for analysis. AUTHORS' CONCLUSIONS: We are uncertain if administration of antibiotics prior to or at the time of ET improves LBR in women undergoing ART based on a single study of 27 women with low-certainty evidence. We are uncertain whether there was a difference in CPR. There was evidence for a reduction in genital tract colonization rates, but the evidence was very low certainty. Data were lacking on other secondary outcomes. The pooled results should be interpreted with caution, due to the small number of women included in the analysis.

Endometriosis research priorities in Australia.

In Australia, endometriosis affects one in nine women and those assigned female at birth. Although endometriosis is more common than conditions such as diabetes, research funding for endometriosis research has historically been low in comparison. The National Action Plan for Endometriosis is an Australian Federal Government initiative designed to redress this imbalance, with a focus on research funding. Identification of research priorities, and subsequent funding allocation that is determined by consumer input is vital. An online survey focusing on Australia and New Zealand found that the highest general priorities were the treatment and management of endometriosis and its cause(s).

Gynaecological and IVF procedures billed through the Medicare Benefits Schedule (MBS) during the COVID-19 pandemic.

BACKGROUND: In response to the COVID-19 pandemic in Australia, restrictions to elective surgeries were implemented nationwide. AIMS: To investigate the response to these restrictions in elective gynaecological and In vitro fertilisation (IVF) procedures during the first wave of the COVID-19 pandemic. MATERIALS AND METHODS: We analysed the Medicare Item Reports for the number of elective gynaecological (labioplasty, vulvoplasty; prolapse and continence; operative hysteroscopy; hysterectomy; fertility) and IVF procedures claimed in Australia between January-June 2020 and compared these to January-June 2019. RESULTS: The number of included gynaecological and IVF procedures performed in January-June 2020 decreased by -13.71% and -12.56%, respectively, compared to January-June 2019. The greatest reductions were in May 2020 (gynaecology -43.71%; IVF -51.63% compared to May 2019), while April 2020 reported decreases of -37.69% and -31.42% in gynaecological and IVF procedures, respectively. In April 2020, 1963 IVF cycle initiations (-45.20% compared to April 2019), 2453 oocyte retrievals (-26.99%) and 3136 embryo transfers (-22.95%) were billed. The procedures with greatest paired monthly decrease were prolapse and continence surgeries in April (676 procedures; -51.85%) and May 2020 (704 procedures; -60.05%), and oocyte retrievals in May 2020 (1637 procedures; -56.70%). CONCLUSIONS: While we observed a decrease in procedural volumes, elective gynaecological and IVF procedures continued in considerable numbers during the restricted timeframes. In the event of future overwhelming biological threat, careful consideration must be given to more effective measures of limiting access for non-emergency procedures to conserve essential resources and reduce risk to both the public and healthcare staff.

Patient-Reported Experiences After Hysterectomy: A Cross-Sectional Study of the Views of Over 2300 Women.

OBJECTIVE: To evaluate women's experiences after hysterectomy and predictors of their contentment and regret with the surgical approaches. METHODS: Cross-sectional, Patient-Reported Experience Measures survey in 2319 Australian women aged 21 to 90 years (median age of 52 years) who had received hysterectomy in the preceding 2 years. RESULTS: Overall, the vast majority of women (>96%) did not regret having had the hysterectomy. Women who received an open abdominal hysterectomy reported slower recovery with about 7% of women still not fully recovered after 12 months compared to those whose surgery was through a less invasive approach. Women who reported no adverse events, having been given a choice of type of hysterectomy, women who received an alternative to open abdominal hysterectomy, and women who felt prepared for discharge from hospital were significantly more likely to be content with their hysterectomy and report positive patient experiences. CONCLUSIONS: Compared with those who received a less invasive approach to hysterectomy, women who received open surgery were more likely to express negative experiences relating to their hospital stay and recovery from surgery. The results inform future improvements of care for women planning a hysterectomy.

Detection of chlamydia infection within human testicular biopsies.

STUDY QUESTION: Can Chlamydia be found in the testes of infertile men? SUMMARY ANSWER: Chlamydia can be found in 16.7% of fresh testicular biopsies and 45.3% of fixed testicular biopsies taken from a selection of infertile men. WHAT IS KNOWN ALREADY: Male chlamydial infection has been understudied despite male and female infections occurring at similar rates. This is particularly true of asymptomatic infections, which occur in 50% of cases. Chlamydial infection has also been associated with increased sperm DNA damage and reduced male fertility. STUDY DESIGN, SIZE, DURATION: We collected diagnostic (fixed, n = 100) and therapeutic (fresh, n = 18) human testicular biopsies during sperm recovery procedures from moderately to severely infertile men in a cross-sectional approach to sampling. PARTICIPANTS/MATERIALS, SETTING, METHODS: The diagnostic and therapeutic biopsies were tested for Chlamydia-specific DNA and protein, using real-time PCR and immunohistochemical approaches, respectively. Serum samples matched to the fresh biopsies were also assayed for the presence of Chlamydia-specific antibodies using immunoblotting techniques. MAIN RESULTS AND THE ROLE OF CHANCE: Chlamydial major outer membrane protein was detected in fixed biopsies at a rate of 45.3%. This was confirmed by detection of chlamydial DNA and TC0500 protein (replication marker). C. trachomatis DNA was detected in fresh biopsies at a rate of 16.7%, and the sera from each of these three positive patients contained C. trachomatis-specific antibodies. Overall, C. trachomatis-specific antibodies were detected in 72.2% of the serum samples from the patients providing fresh biopsies, although none of the patients were symptomatic nor had they reported a previous sexually transmitted infection diagnosis including Chlamydia. LIMITATIONS, REASONS FOR CAUTION: No reproductively healthy male testicular biopsies were tested for the presence of Chlamydia DNA or proteins or Chlamydia-specific antibodies due to the unavailability of these samples. WIDER IMPLICATIONS FOR THE FINDINGS: Application of Chlamydia-specific PCR and immunohistochemistry in this human male infertility context of testicular biopsies reveals evidence of a high prevalence of previously unrecognised infection, which may potentially have a pathogenic role in spermatogenic failure. STUDY FUNDING/COMPETING INTEREST(S): Funding for this project was provided by the Australian NHMRC under project grant number APP1062198. We also acknowledge assistance from the Monash IVF Group and Queensland Fertility Group in the collection of fresh biopsies, and the Monash Health and co-author McLachlan (declared equity interest) in retrieval and sectioning of fixed biopsies. E.M. declares an equity interest in the study due to financing of fixed biopsy sectioning. All other authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Advanced sperm selection techniques for assisted reproduction.

BACKGROUND: Assisted reproductive technologies (ART) including in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), combine gametes to enhance the probability of fertilisation and pregnancy. Advanced sperm selection techniques are increasingly employed in ART, most commonly in cycles utilising ICSI. Advanced sperm selection techniques are proposed to improve the chance that structurally intact and mature sperm with high DNA integrity are selected for fertilisation. Strategies include selection according to surface charge; sperm apoptosis; sperm birefringence; ability to bind to hyaluronic acid; and sperm morphology under ultra-high magnification. These techniques are intended to improve ART outcomes. OBJECTIVES: To evaluate the effectiveness and safety of advanced sperm selection techniques on ART outcomes. SEARCH METHODS: We conducted a systematic search of electronic databases (Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL via the Cochrane Register of Studies Online, MEDLINE, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL); trials registers (ClinicalTrials.gov, Current Controlled Trials, and the World Health Organization International Clinical Trials Registry Platform); conference abstracts (Web of Knowledge); and grey literature (OpenGrey) for relevant randomised controlled trials (RCTs). We handsearched the reference lists of included studies and similar reviews. The search was conducted in June 2018. SELECTION CRITERIA: We included RCTs comparing advanced sperm selection techniques versus standard IVF, ICSI, or another technique. We excluded studies of intracytoplasmic morphologically selected sperm injection (IMSI), as they are subject to a separate Cochrane Review. Primary outcomes measured were live birth and miscarriage per woman randomly assigned. Secondary outcome measures included clinical pregnancy per woman randomly assigned. Secondary adverse events measured included miscarriage per clinical pregnancy and foetal abnormality. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility and risk of bias and extracted data. Any disagreements were resolved by consultation with a third review author. We consulted study investigators to resolve queries. Risk ratios (RRs) were calculated with 95% confidence intervals (CIs). We combined studies using a fixed-effect model. We evaluated the quality of the evidence using GRADE methods. MAIN RESULTS: We included eight RCTs (4147 women). The quality of evidence ranged from very low to low. The main limitations were imprecision, performance bias, and attrition bias.Hyaluronic acid selected sperm-intracytoplasmic sperm injection (HA-ICSI) compared to ICSITwo RCTs compared the effects of HA-ICSI versus ICSI on live birth. The quality of the evidence was low. There may be little or no difference between groups: 25% chance of live birth with ICSI versus 24.5% to 31% with HA-ICSI (RR 1.09, 95% CI 0.97 to 1.23, 2903 women, I2 = 0%, low-quality evidence). Three RCTs reported on miscarriage. HA-ICSI may decrease miscarriage per woman randomly assigned: 7% chance of miscarriage with ICSI versus 3% to 6% chance with HA-ICSI (RR 0.61, 95% CI 0.45 to 0.83, 3005 women, I2 = 0%, low-quality evidence) and per clinical pregnancy: 20% chance of miscarriage with ICSI compared to 9% to 16% chance with HA-ICSI (RR 0.62, 95% CI 0.46 to 0.82, 1065 women, I2 = 0%, low-quality evidence). Four RCTs reported on clinical pregnancy. There may be little or no difference between groups: 37% chance of pregnancy with ICSI versus 34% to 40% chance with HA-ICSI (RR 1.00, 95% CI 0.92 to 1.09, 3492 women, I2 = 0%, low-quality evidence).HA-ICSI compared to SpermSlowOne RCT compared HA-ICSI to SpermSlow. The quality of the evidence was very low. We are uncertain whether HA-ICSI improves live birth compared to SpermSlow (RR 1.13, 95% CI 0.64 to 2.01, 100 women) or clinical pregnancy (RR 1.05, 95% CI 0.66 to 1.68, 100 women). We are uncertain whether HA-ICSI reduces miscarriage per woman (RR 0.80, 95% CI 0.23 to 2.81, 100 women) or per clinical pregnancy (RR 0.76, 95% CI 0.24 to 2.44, 41 women).Magnetic-activated cell sorting (MACS) compared to ICSIOne RCT compared MACS to ICSI for live birth; three reported clinical pregnancy; and two reported miscarriage. The quality of the evidence was very low. We are uncertain whether MACS improves live birth (RR 1.95, 95% CI 0.89 to 4.29, 62 women) or clinical pregnancy (RR 1.05, 95% CI 0.84 to 1.31, 413 women, I2 = 81%). We are also uncertain if MACS reduces miscarriage per woman (RR 0.95, 95% CI 0.16 to 5.63, 150 women, I2 = 0%) or per clinical pregnancy (RR 0.51, 95%CI 0.09 to 2.82, 53 women, I2=0)Zeta sperm selection compared to ICSIOne RCT evaluated Zeta sperm selection. The quality of the evidence was very low. We are uncertain of the effect of Zeta sperm selection on live birth (RR 2.48, 95% CI 1.34 to 4.56, 203 women) or clinical pregnancy (RR 1.82, 95% CI 1.20 to 2.75, 203 women). We are also uncertain if Zeta sperm selection reduces miscarriage per woman (RR 0.73, 95% CI 0.16 to 3.37, 203 women) or per clinical pregnancy (RR 0.41, 95% CI 0.10 to 1.68, 1 RCT, 62 women).MACS compared to HA-ICSIOne RCT compared MACS to HA-ICSI. This study did not report on live birth. The quality of the evidence was very low. We are uncertain of the effect on miscarriage per woman (RR 1.52, 95% CI 0.10 to 23.35, 78 women) or per clinical pregnancy (RR 1.06, 95% CI 0.07 to 15.64, 37 women). We are also uncertain of the effect on clinical pregnancy (RR 1.44, 95% CI 0.91 to 2.27, 78 women). AUTHORS' CONCLUSIONS: The evidence suggests that sperm selected by hyaluronic acid binding may have little or no effect on live birth or clinical pregnancy but may reduce miscarriage. We are uncertain of the effect of Zeta sperm selection on live birth, clinical pregnancy, and miscarriage due principally to the very low quality of the evidence for this intervention. We are uncertain of the effect of the other selection techniques on live birth, miscarriage, or pregnancy.Further high-quality studies, including the awaited data from the identified ongoing studies, are required to evaluate whether any of these advanced sperm selection techniques can be recommended for use in routine practice.

Antioxidants for male subfertility.

BACKGROUND: The inability to have children affects 10% to 15% of couples worldwide. A male factor is estimated to account for up to half of the infertility cases with between 25% to 87% of male subfertility considered to be due to the effect of oxidative stress. Oral supplementation with antioxidants is thought to improve sperm quality by reducing oxidative damage. Antioxidants are widely available and inexpensive when compared to other fertility treatments, however most antioxidants are uncontrolled by regulation and the evidence for their effectiveness is uncertain. We compared the benefits and risks of different antioxidants used for male subfertility. This review did not examine the use of antioxidants in normospermic men. OBJECTIVES: To evaluate the effectiveness and safety of supplementary oral antioxidants in subfertile men. SEARCH METHODS: The Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and two trials registers were searched on 1 February 2018, together with reference checking and contact with study authors and experts in the field to identify additional trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared any type, dose or combination of oral antioxidant supplement with placebo, no treatment or treatment with another antioxidant, among subfertile men of a couple attending a reproductive clinic. We excluded studies comparing antioxidants with fertility drugs alone and studies that included fertile men attending a fertility clinic because of female partner infertility. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. The primary review outcome was live birth. Clinical pregnancy, adverse events and sperm parameters were secondary outcomes. MAIN RESULTS: We included 61 studies with a total population of 6264 subfertile men, aged between 18 and 65 years, part of a couple who had been referred to a fertility clinic and some of whom were undergoing assisted reproductive techniques (ART). Investigators compared and combined 18 different oral antioxidants. The evidence was of 'low' to 'very low' quality: the main limitation was that out of the 44 included studies in the meta-analysis only 12 studies reported on live birth or clinical pregnancy. The evidence is current up to February 2018.Live birth: antioxidants may lead to increased live birth rates (OR 1.79, 95% CI 1.20 to 2.67, P = 0.005, 7 RCTs, 750 men, I2 = 40%, low-quality evidence). Results suggest that if in the studies contributing to the analysis of live birth rate, the baseline chance of live birth following placebo or no treatment is assumed to be 12%, the chance following the use of antioxidants is estimated to be between 14% and 26%. However, this result was based on only 124 live births from 750 couples in seven relatively small studies. When studies at high risk of bias were removed from the analysis, there was no evidence of increased live birth (Peto OR 1.38, 95% CI 0.89 to 2.16; participants = 540 men, 5 RCTs, P = 0.15, I2 = 0%).Clinical pregnancy rate: antioxidants may lead to increased clinical pregnancy rates (OR 2.97, 95% CI 1.91 to 4.63, P < 0.0001, 11 RCTs, 786 men, I2 = 0%, low-quality evidence) compared to placebo or no treatment. This suggests that if in the studies contributing to the analysis of clinical pregnancy, the baseline chance of clinical pregnancy following placebo or no treatment is assumed to be 7%, the chance following the use of antioxidants is estimated to be between 12% and 26%. This result was based on 105 clinical pregnancies from 786 couples in 11 small studies.Adverse eventsMiscarriage: only three studies reported on this outcome and the event rate was very low. There was no difference in miscarriage rate between the antioxidant and placebo or no treatment group (OR 1.74, 95% CI 0.40 to 7.60, P = 0.46, 3 RCTs, 247 men, I2 = 0%, very low-quality evidence). The findings suggest that in a population of subfertile men with an expected miscarriage rate of 2%, the chance following the use of an antioxidant would result in the risk of a miscarriage between 1% and 13%.Gastrointestinal: antioxidants may lead to an increase in mild gastrointestinal upsets when compared to placebo or no treatment (OR 2.51, 95% CI 1.25 to 5.03, P = 0.010, 11 RCTs, 948 men, I2 = 50%, very low-quality evidence). This suggests that if the chance of gastrointestinal upsets following placebo or no treatment is assumed to be 2%, the chance following the use of antioxidants is estimated to be between 2% and 9%. However, this result was based on a low event rate of 35 out of 948 men in 10 small or medium-sized studies, and the quality of the evidence was rated very low and was high in heterogeneity.We were unable to draw any conclusions from the antioxidant versus antioxidant comparison as insufficient studies compared the same interventions. AUTHORS' CONCLUSIONS: In this review, there is low-quality evidence from seven small randomised controlled trials suggesting that antioxidant supplementation in subfertile males may improve live birth rates for couples attending fertility clinics. Low-quality evidence suggests that clinical pregnancy rates may also increase. Overall, there is no evidence of increased risk of miscarriage, however antioxidants may give more mild gastrointestinal upsets but the evidence is of very low quality. Subfertilte couples should be advised that overall, the current evidence is inconclusive based on serious risk of bias due to poor reporting of methods of randomisation, failure to report on the clinical outcomes live birth rate and clinical pregnancy, often unclear or even high attrition, and also imprecision due to often low event rates and small overall sample sizes. Further large well-designed randomised placebo-controlled trials reporting on pregnancy and live births are still required to clarify the exact role of antioxidants.

Changes in the incidence and uptake of reproductive surgery versus in vitro fertilisation in Australia between 2001 and 2015: A population-based study.

OBJECTIVE: Improvements in success rates of assisted reproduction led to predictions that infertility surgery in both women and men would become extinct in developed countries. We sought to identify the changes in reproductive surgery that occurred between 2001 and 2015 to determine whether these predictions have been accurate. DESIGN: The Australian Institute of Health and Welfare (AIHW) national procedural dataset and the Australian Medicare Benefits Scheme (MBS) claims database were searched for procedure data for male and female reproductive surgery and assisted reproduction from January 2001 to December 2015. The denominators were based on annual point estimates of the total population aged 25-44 years (female) and 25-55 years (male) from the Australian Bureau of Statistics (ABS). This dataset provides procedures undertaken but not their indications. RESULTS: Over the study period the incidence of tubal surgery fell by 66%, vasectomy reversal by 33%, and surgical varicocoelectomy by 50%. In contrast, the rate of hysteroscopic myomectomy increased by 48%, hysteroscopic septoplasty by 125%, and laparoscopy for severe endometriosis increased by 84%. In vitro fertilisation oocyte retrievals increased by 90%. The rate of abdominal myomectomy was unchanged. CONCLUSION: Fertility surgery is not dead but has evolved.

Surgical approach to hysterectomy and barriers to using minimally invasive methods.

Minimally invasive approaches to hysterectomy have been shown to be safe, effective and have recovery advantages over open hysterectomy, yet in Australia 36% of hysterectomies are still conducted by open surgery. In 2006, a survey of Australian gynaecological specialists found the main impediment to increasing laparoscopic hysterectomy to be a lack of surgical skills training opportunities. We resurveyed specialists to explore contemporary factors influencing surgeons' approaches to hysterectomy; 258 (estimated ~19%) provided analysable responses. Despite >50% of surveyed specialists wishing to practise laparoscopic hysterectomy in the future, lack of surgical skills, arising from the lack of training opportunities, remains the main impediment.

Factors influencing women's decision making in hysterectomy.

OBJECTIVE: To explore factors influencing how well-informed women felt about hysterectomy, influences on their decision making, and on them receiving a less-invasive alternative to open surgery. METHODS: Online questionnaire, conducted in 2015-2016, of women who had received a hysterectomy in Australia, in the preceding two years. RESULTS: Questionnaires were completed by 2319/6000 women (39% response). Most women (n=2225; 96%) felt well-informed about hysterectomy. Women were more aware of the open abdominal approach (n=1798; 77%), than of less-invasive vaginal (n=1552; 67%), laparoscopic (n=1540; 66%), laparoscopic-assisted (n=1303; 56%), and robotic approaches (n=289; 12%). Most women (n=1435; 62%) reported their gynaecologist was the most influential information source. Women who received information about hysterectomy from a GP (OR=1.47; 95% CI 1.15-1.90), or from a gynaecologist (OR=1.3; 95% CI 1.06-1.58), were more likely to feel better informed (p<0.01). CONCLUSION: This study is important because it helps clinicians, researchers and health policy makers to understand why many women still receive an open abdominal approach despite many learned societies recommending to avoid it if possible. PRACTICE IMPLICATIONS: Additional information, or education about avoiding open abdominal approach where possible may lead to a greater number of women receiving less-invasive types of hysterectomy in the future.

Surgery or in vitro fertilization: The simplicity of this question belies its complexity.

Unlike surgery, assisted reproduction, particularly in vitro fertilisation (IVF), requires a low skill base, is largely practitioner independent, is highly effective, quality controlled, reproducible and consistent in the management of endometriosis-associated infertility. Ultimately, however, the decision to proceed to IVF or surgery is dependent on the woman, her reproductive expectations, her specific disease pattern, her support and family network and the resources available in a given health care setting.

Incidence of transmissible diseases in a network of assisted reproduction clinics throughout Queensland.

In assisted reproduction, knowledge of the presence of transmissible disease assists diagnosis and permits appropriate risk minimisation. The overall incidence was lowest in the Brisbane full-cost clinic and highest in the Springwood low-cost clinic. Male partners predominated over females, particularly in the low-cost clinic. Hepatitis C was the most commonly detected infection with the highest incidence in the low-cost clinic. HIV was the least commonly detected infection amongst those tested.

Antioxidants for male subfertility.

BACKGROUND: Between 30% to 80% of male subfertility cases are considered to be due to the damaging effects of oxidative stress on sperm and 1 man in 20 will be affected by subfertility. Antioxidants are widely available and inexpensive when compared to other fertility treatments and many men are already using these to improve their fertility. It is thought that oral supplementation with antioxidants may improve sperm quality by reducing oxidative stress. Pentoxifylline, a drug that acts like an antioxidant, was also included in this review.   OBJECTIVES: This Cochrane review aimed to evaluate the effectiveness and safety of oral supplementation with antioxidants for subfertile male partners in couples seeking fertility assistance. SEARCH METHODS: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO and AMED databases (from inception until January 2014); trial registers; sources of unpublished literature and reference lists. An updated search was run in August 2014 when potentially eligible studies were placed in 'Studies awaiting assessment'. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing any type or dose of antioxidant supplement (single or combined) taken by the subfertile male partner of a couple seeking fertility assistance with a placebo, no treatment or another antioxidant. DATA COLLECTION AND ANALYSIS: Two review authors independently selected eligible studies, extracted the data and assessed the risk of bias of the included studies. The primary review outcome was live birth; secondary outcomes included clinical pregnancy rates, adverse events, sperm DNA fragmentation, sperm motility and concentration. Data were combined, where appropriate, to calculate pooled odds ratios (ORs) or mean differences (MD) and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I(2) statistic. We assessed the overall quality of the evidence for the main outcomes using GRADE methods.   MAIN RESULTS: This updated review included 48 RCTs that compared single and combined antioxidants with placebo, no treatment or another antioxidant in a population of 4179 subfertile men. The duration of the trials ranged from 3 to 26 weeks with follow up ranging from 3 weeks to 2 years. The men were aged from 20 to 52 years. Most of the men enrolled in these trials had low total sperm motility and sperm concentration. One study enrolled men after varicocelectomy, one enrolled men with a varicocoele, and one recruited men with chronic prostatitis. Three trials enrolled men who, as a couple, were undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) and one trial enrolled men who were part of a couple undergoing intrauterine insemination (IUI). Funding sources were stated by 15 trials. Four of these trials stated that funding was from a commercial source and the remaining 11 obtained funding through non-commercial avenues or university grants. Thirty-three trials did not report any funding sources.A limitation of this review was that in a sense we had included two different groups of trials, those that reported on the use of antioxidants and the effect on live birth and clinical pregnancy, and a second group that reported on sperm parameters as their primary outcome and had no intention of reporting the primary outcomes of this review. We included 25 trials reporting on sperm parameters and only three of these reported on live birth or clinical pregnancy. Other limitations included poor reporting of study methods, imprecision, the small number of trials providing usable data, the small sample size of many of the included studies and the lack of adverse events reporting. The evidence was graded as 'very low' to 'low'. The data were current to 31 January 2014.Live birth: antioxidants may have increased live birth rates (OR 4.21, 95% CI 2.08 to 8.51, P< 0.0001, 4 RCTs, 277 men, I(2) = 0%, low quality evidence). This suggests that if the chance of a live birth following placebo or no treatment is assumed to be 5%, the chance following the use of antioxidants is estimated to be between 10% and 31%. However, this result was based on only 44 live births from a total of 277 couples in four small studies.Clinical pregnancy rate: antioxidants may have increased clinical pregnancy rates (OR 3.43, 95% CI 1.92 to 6.11, P < 0.0001, 7 RCTs, 522 men, I(2) = 0%, low quality evidence). This suggests that if the chance of clinical pregnancy following placebo or no treatment is assumed to be 6%, the chance following the use of antioxidants is estimated at between 11% and 28%. However, there were only seven small studies in this analysis and the quality of the evidence was rated as low.Miscarriage: only three trials reported on this outcome and the event rate was very low. There was insufficient evidence to show whether there was a difference in miscarriage rates between the antioxidant and placebo or no treatment groups (OR 1.74, 95% CI 0.40 to 7.60, P = 0.46, 3 RCTs, 247 men, I(2) = 0%, very low quality evidence). The findings suggest that in a population of subfertile men with an expected miscarriage rate of 2%, use of an antioxidant would result in the risk of a miscarriage lying between 1% and 13%.Gastrointestinal upsets: there was insufficient evidence to show whether there was a difference in gastrointestinal upsets when antioxidants were compared to placebo or no treatment as the event rate was very low (OR 1.60, 95% CI 0.47 to 5.50, P = 0.46, 6 RCTs, 429 men, I(2) = 0%).We were unable to draw any conclusions from the antioxidant versus antioxidant comparison as not enough trials compared the same interventions. AUTHORS' CONCLUSIONS: There is low quality evidence from only four small randomised controlled trials suggesting that antioxidant supplementation in subfertile males may improve live birth rates for couples attending fertility clinics. Low quality evidence suggests that clinical pregnancy rates may increase. There is no evidence of increased risk of miscarriage but this is uncertain as the evidence is of very low quality. Data were lacking on other adverse effects. Further large well-designed randomised placebo-controlled trials are needed to clarify these results.

Advanced sperm selection techniques for assisted reproduction.

BACKGROUND: Assisted reproductive technologies (ART) such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) bring together gametes outside of the body to enhance the probability of fertilisation and pregnancy. Advanced sperm selection techniques are increasingly being employed in ART, most commonly in cycles utilising ICSI. Advanced sperm selection techniques are thought to improve the chance that structurally intact and mature sperm with high DNA integrity are selected for fertilisation. Advanced sperm selection strategies include selection according to surface charge; sperm apoptosis; sperm birefringence; ability to bind to hyaluronic acid; and sperm morphology under ultra-high magnification. These techniques theoretically improve ART outcomes. OBJECTIVES: To evaluate the impact of advanced sperm selection techniques on ART outcomes. SEARCH METHODS: Systematic search of electronic databases (Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Latin American and Caribbean Health Science Information Database (LILACS)), trials registers (ClinicalTrials.gov, Current Controlled Trials, World Health Organization International Clinical Trials Registry Platform), conference abstracts (Web of Knowledge) and grey literature (OpenGrey) for relevant randomised controlled trials. We handsearched the reference lists of included studies and similar reviews. The search was conducted in May 2014. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing an advanced sperm selection technique versus standard IVF or ICSI or versus another advanced sperm selection technique. We excluded studies of sperm selection using ultra-high magnification (intracytoplasmic morphologically selected sperm injection, or IMSI), as they are the subject of a separate Cochrane review. Quasi-randomised and pseudo-randomised trials were excluded. Our primary outcome measure was live birth rate per woman randomly assigned. Secondary outcome measures included clinical pregnancy per woman randomly assigned, miscarriage per clinical pregnancy and fetal abnormality per clinical pregnancy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility of studies and risk of bias, and performed data extraction. Disagreements were resolved by consultation with a third review author. Study investigators were consulted to resolve other queries that arose. Risk ratios (RRs) were calculated with 95% confidence intervals (CIs). We planned to combine studies using a fixed-effect model, if sufficient data were available. The quality of the evidence was evaluated using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methods. MAIN RESULTS: Two RCTs were included in the review. Both evaluated sperm selection by hyaluronanic acid binding for ICSI, but only one reported live births. No studies were identified that were related to surface charge selection, sperm apoptosis or sperm birefringence.One RCT compared hyaluronanic acid binding versus conventional ICSI. Live birth was not reported. Evidence was insufficient to show whether there was a difference between groups in clinical pregnancy rates (RR 1.01, 95% CI 0.84 to 1.22, one RCT, 482 women). This evidence was deemed to be of low quality, mainly as the result of poor reporting of methods and findings. Miscarriage data were unclear, and fetal abnormality rates were not reported.The other RCT compared two different hyaluronanic acid binding techniques, SpermSlow and physiological intracytoplasmic sperm injection (PISCI). Evidence was insufficient to indicate whether there was a difference between groups in rates of live birth (RR 1.16, 95% CI 0.65 to 2.05, one RCT, 99 women), clinical pregnancy (RR 1.07, 95% CI 0.67 to 1.71, one RCT, 99 women) or miscarriage (RR 0.76, 95% CI 0.24 to 2.44, one RCT, 41 women). The evidence for these comparisons was deemed to be of low quality, as it was limited by imprecision and poor reporting of study methods. Fetal abnormality rates were not reported. AUTHORS' CONCLUSIONS: Evidence was insufficient to allow review authors to determine whether sperm selected by hyaluronanic acid binding improve live birth or pregnancy outcomes in ART, and no clear data on adverse effects were available. Evidence was also insufficient to show whether there is a difference in efficacy between the hyaluronic acid binding methods SpermSlow and PICSI. No randomised evidence evaluating sperm selection by sperm apoptosis, sperm birefringence or surface charge was found.Further studies of suitable quality are required to evaluate whether any of these advanced sperm selection techniques can be recommended for use in clinical practice.

Clomiphene ovulation induction and higher-order multiple pregnancy.

Clomiphene citrate is a widely used treatment for ovulatory dysfunction in women seeking pregnancy. The major adverse consequence of clomiphene use is the increased risk of multiple and higher-order multiple pregnancy. Mechanisms for multiple pregnancy include dosing variation, adjuvant therapies, pretreatment weight loss and a cumulative effect of multiple clomiphene cycles. It has been suggested that the risk of higher-order multiple pregnancy may be reduced with ultrasound monitoring, although there is limited evidence to support this practice.