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 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)

Advanced sperm selection techniques for assisted reproduction (Review)

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

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

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

© 2018 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists 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

Sperm DNA fragmentation in men with malignancy

Objective: To determine if men with malignancy have increased sperm DNA fragmentation compared with men presenting for sperm donation. Design: Retrospective observational study. Setting: Tertiary-level fertility center. Patient(s): Eighty-nine men with cancer presenting for prophylactic semen cryopreservation and 35 men presenting for sperm donation. Intervention(s): None. Main Outcome Measure(s): Sperm DNA fragmentation index (DFI) measured by sperm chromatin assay. Result(s): The mean sperm DFI in men with a diagnosis of cancer, 9.88% (95% confidence interval [CI] 7.84%-12.44%), did not differ from that found in men presenting for sperm donation 10.46% (95% CI 8.68%-11.80%). There were no significant differences in mean sperm DFI within cancer subgroups or when comparing testicular and nontesticular cancers. Subgroup analysis lacked statistical power. Men with testicular cancer have significantly reduced sperm concentration compared with both control subjects and men with nontesticular cancer. Conclusion(s): In our study population there was no difference in sperm DFI between men undergoing prophylactic semen cryopreservation and men presenting for sperm donation. Sperm DFI assessment has limited utility in the routine evaluation of men presenting for semen cryopreservation

Antibiotics prior to embryo transfer in ART (Review)

Embryo transfer (ET) involves the placement of one or more embryos into the uterine cavity, usually by passing a catheter through the cervical os. ET is the final step in an assisted reproductive technology (ART) cycle, where a woman has undergone controlled ovarian stimulation, egg retrieval and in vitro fertilisation of her eggs. Despite the transfer of high quality embryos, many ETs do not result in a pregnancy. There are many factors which may affect the success of ET, including the presence of upper genital tract microbial colonisation. The administration of antibiotics prior to ET has been suggested as an intervention to reduce levels of microbial colonisation and hence improve pregnancy rates.To evaluate the effectiveness and safety of antibiotic administration prior to ET during ART cycles.We searched the Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library, MEDLINE, Ovid MEDLINE® In-Process & Other Non-Indexed Citations, Ovid MEDLINE® Daily and Ovid MEDLINE® (from inception to February 2011), Ovid EMBASE (January 2010 to February 2011), Ovid PsycINFO, CINAHL, LILACS, trial registers for ongoing and registered trials, citation indexes, ClinicalStudyResults, PubMed, OpenSIGLE database and for for herbal and complimentary therapy protocols and reviews.Only randomised controlled trials were included.The titles and abstracts of articles identified by the search were screened by one review author for eligibility. Two review authors then independently examined the full text articles for suitability for inclusion in the review. Data were extracted independently by two review authors.We identified four potential studies, of which three were excluded.The included trial reported clinical pregnancy rates but not live births. There was no evidence of a difference in clinical pregnancy rate between those receiving an amoxycillin and clavulanic acid antibiotic combination (64/178: 36%) and those not (61/172: 35.5%) (OR1.02, 95% CI 0.66 to 1.58). Genital tract colonisation was significantly reduced in women receiving this antibiotic regimen (OR 0.59, 95% CI 0.37 to 0.95).This review suggests that the administration of amoxycillin and clavulanic acid prior to embryo transfer reduced upper genital tract microbial contamination but did not alter clinical pregnancy rates. The effect of this intervention on live birth is unknown. There are no data from randomised controlled trials to support or refute other antibiotic regimens in this setting.Future research is warranted to assess the efficacy of alternative antibiotic regimens. Researchers should assess live birth as the primary outcome and address quantitative microbial colonization as a secondary outcome

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 ICSI Two 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, I = 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, I = 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, I = 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, I = 0%, low-quality evidence). HA-ICSI compared to SpermSlow One 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 ICSI One 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, I = 81%). We are also uncertain if MACS reduces miscarriage per woman (RR 0.95, 95% CI 0.16 to 5.63, 150 women, I = 0%) or per clinical pregnancy (RR 0.51, 95%CI 0.09 to 2.82, 53 women, I =0) Zeta sperm selection compared to ICSI One 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-ICSI One 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

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.</p