Androgens (dehydroepiandrosterone or testosterone) for women undergoing assisted reproduction.

BACKGROUND: Practitioners in the field of assisted reproductive technology (ART) continually seek alternative or adjunct treatments to improve ART outcomes. This Cochrane review investigates the adjunct use of synthetic versions of two naturally produced hormones, dehydroepiandrosterone (DHEA) and testosterone (T), in assisted reproduction. Steroid hormones are proposed to increase conception rates by positively affecting follicular response to gonadotrophin stimulation. This may lead to a greater oocyte yield and, subsequently, an increased chance of pregnancy. OBJECTIVES: To assess the effectiveness and safety of DHEA and T as pre- or co-treatments in infertile women undergoing assisted reproduction. SEARCH METHODS: We searched the following electronic databases up to 8 January 2024: the Gynaecology and Fertility Group (CGF) Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, and trial registries for ongoing trials. We also searched citation indexes, Web of Science, PubMed, and OpenGrey. We searched the reference lists of relevant studies and contacted experts in the field for any additional trials. There were no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing DHEA or T as an adjunct treatment to any other active intervention, placebo, or no treatment in women undergoing assisted reproduction. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted relevant data, and assessed risk of bias. We pooled data from studies using fixed-effect models. We calculated odds ratios (ORs) for each dichotomous outcome. Analyses were stratified by type of treatment. We assessed the certainty of evidence for the main findings using GRADE methods. MAIN RESULTS: We included 29 RCTs. There were 1599 women in the intervention group and 1469 in the control group. Apart from three trials, the trial participants were women identified as 'poor responders' to standard in vitro fertilisation (IVF) protocols. The included trials compared either T or DHEA treatment with placebo or no treatment. Pre-treatment with DHEA versus placebo/no treatment: DHEA likely results in little to no difference in live birth/ongoing pregnancy rates (OR 1.30, 95% confidence interval (CI) 0.95 to 1.76; I² = 16%, 9 RCTs, N = 1433, moderate certainty evidence). This suggests that in women with a 12% chance of live birth/ongoing pregnancy with placebo or no treatment, the live birth/ongoing pregnancy rate in women using DHEA will be between 12% and 20%. DHEA likely does not decrease miscarriage rates (OR 0.85, 95% CI 0.53 to 1.37; I² = 0%, 10 RCTs, N =1601, moderate certainty evidence). DHEA likely results in little to no difference in clinical pregnancy rates (OR 1.18, 95% CI 0.93 to 1.49; I² = 0%, 13 RCTs, N = 1886, moderate certainty evidence). This suggests that in women with a 17% chance of clinical pregnancy with placebo or no treatment, the clinical pregnancy rate in women using DHEA will be between 16% and 24%. We are very uncertain about the effect of DHEA on multiple pregnancy (OR 3.05, 95% CI 0.47 to 19.66; 7 RCTs, N = 463, very low certainty evidence). Pre-treatment with T versus placebo/no treatment: T likely improves live birth rates (OR 2.53, 95% CI 1.61 to 3.99; I² = 0%, 8 RCTs, N = 716, moderate certainty evidence). This suggests that in women with a 10% chance of live birth with placebo or no treatment, the live birth rate in women using T will be between 15% and 30%. T likely does not decrease miscarriage rates (OR 1.63, 95% CI 0.76 to 3.51; I² = 0%, 9 RCTs, N = 755, moderate certainty evidence). T likely increases clinical pregnancy rates (OR 2.17, 95% CI 1.54 to 3.06; I² = 0%, 13 RCTs, N = 1152, moderate certainty evidence). This suggests that in women with a 12% chance of clinical pregnancy with placebo or no treatment, the clinical pregnancy rate in women using T will be between 17% and 29%. We are very uncertain about the effect of T on multiple pregnancy (OR 2.56, 95% CI 0.59 to 11.20; 5 RCTs, N = 449, very low certainty evidence). We are uncertain about the effect of T versus oestradiol or T versus oestradiol + oral contraceptive pills. The certainty of the evidence was moderate to very low, the main limitations being lack of blinding in the included trials, inadequate reporting of study methods, and low event and sample sizes in the trials. Data on adverse events were sparse; any reported events were minor. AUTHORS' CONCLUSIONS: Pre-treatment with T likely improves, and pre-treatment with DHEA likely results in little to no difference, in live birth and clinical pregnancy rates in women undergoing IVF who have been identified as poor responders. DHEA and T probably do not decrease miscarriage rates in women under IVF treatment. The effects of DHEA and T on multiple pregnancy are uncertain. Data regarding adverse events were very limited; any reported events were minor. Research is needed to identify the optimal duration of treatment with T. Future studies should include data collection on adverse events and multiple pregnancy.

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.

Non-directed postmortem sperm donation: some questions.

In their recent 'The ethical case for non-directed postmortem sperm donation', Hodson and Parker outline and defend the concept of voluntary non-directed postmortem sperm donation, the idea that men should be able to register their desire to donate their sperm after death for use by strangers since this would offer a potential means of increasing the quantity and heterogeneity of donor sperm. In this response, we raise some concerns about their proposal, focusing in particular on the fact that current methodologies do not make for a reliable way of ensuring that sperm retrieved postmortem has a good chance of leading to conception, which is in turn likely to make potential recipients reluctant to use such sperm. These concerns add to the ethical doubts that attend aspects of the proposal, making the prospect of implementation of such a policy unlikely at best.

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.

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.

Androgens (dehydroepiandrosterone or testosterone) for women undergoing assisted reproduction.

BACKGROUND: Infertility is a condition affecting 10% to 15% of couples of reproductive age. It is generally defined as "the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse". The treatment of infertility may involve manipulation of gametes or of the embryos themselves. These techniques are together known as assisted reproductive technology (ART). Practitioners are constantly seeking alternative or adjunct treatments, or both, in the hope that they may improve the outcome of assisted reproductive techniques. This Cochrane review focusses on the adjunct use of synthetic versions of two naturally-produced hormones, dehydroepiandrosterone (DHEA) and testosterone (T), in assisted reproduction.DHEA and its derivative testosterone are steroid hormones proposed to increase conception rates by positively affecting follicular response to gonadotrophin stimulation, leading to greater oocyte yields and, in turn, increased chance of pregnancy. OBJECTIVES: To assess the effectiveness and safety of DHEA and testosterone as pre- or co-treatments in subfertile women undergoing assisted reproduction. SEARCH METHODS: We searched the following electronic databases, trial registers and websites up to 12 March 2015: the Cochrane Central Register of Controlled Trials (CENTRAL), the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, MEDLINE, EMBASE, PsycINFO, CINAHL, electronic trial registers for ongoing and registered trials, citation indexes, conference abstracts in the Web of Science, PubMed and OpenSIGLE. We also carried out handsearches. There were no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing DHEA or testosterone as an adjunct treatment to any other active intervention, placebo, or no treatment in women undergoing assisted reproduction. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted relevant data and assessed them for risk of bias. We pooled studies using fixed-effect models. We calculated odds ratios (ORs) for each dichotomous outcome. Analyses were stratified by type of treatment. There were no data for the intended groupings by dose, mode of delivery or after one/more than one cycle.We assessed the overall quality of the evidence for the main findings using the GRADE working group methods. MAIN RESULTS: We included 17 RCTs with a total of 1496 participants. Apart from two trials, the trial participants were women identified as 'poor responders' to standard IVF protocols. The included trials compared either testosterone or DHEA treatment with placebo or no treatment.When DHEA was compared with placebo or no treatment, pre-treatment with DHEA was associated with higher rates of live birth or ongoing pregnancy (OR 1.88, 95% CI 1.30 to 2.71; eight RCTs, N = 878, I² statistic = 27%, moderate quality evidence). This suggests that in women with a 12% chance of live birth/ongoing pregnancy with placebo or no treatment, the live birth/ongoing pregnancy rate in women using DHEA will be between 15% and 26%. However, in a sensitivity analysis removing trials at high risk of performance bias, the effect size was reduced and no longer reached significance (OR 1.50, 95% CI 0.88 to 2.56; five RCTs, N = 306, I² statistic = 43%). There was no evidence of a difference in miscarriage rates (OR 0.58, 95% CI 0.29 to 1.17; eight RCTs, N = 950, I² statistic = 0%, moderate quality evidence). Multiple pregnancy data were available for five trials, with one multiple pregnancy in the DHEA group of one trial (OR 3.23, 95% CI 0.13 to 81.01; five RCTs, N = 267, very low quality evidence).When testosterone was compared with placebo or no treatment we found that pre-treatment with testosterone was associated with higher live birth rates (OR 2.60, 95% CI 1.30 to 5.20; four RCTs, N = 345, I² statistic = 0%, moderate evidence). This suggests that in women with an 8% chance of live birth with placebo or no treatment, the live birth rate in women using testosterone will be between 10% and 32%. On removal of studies at high risk of performance bias in a sensitivity analysis, the remaining study showed no evidence of a difference between the groups (OR 2.00, 95% CI 0.17 to 23.49; one RCT, N = 53). There was no evidence of a difference in miscarriage rates (OR 2.04, 95% CI 0.58 to 7.13; four RCTs, N = 345, I² = 0%, low quality evidence). Multiple pregnancy data were available for three trials, with four events in the testosterone group and one in the placebo/no treatment group (OR 3.09, 95% CI 0.48 to 19.98; three RCTs, N = 292, very low quality evidence).One study compared testosterone with estradiol and reported no evidence of a difference in live birth rates (OR 2.06, 95% CI 0.43 to 9.87; one RCT, N = 46, very low quality evidence) or miscarriage rates (OR 0.70, 95% CI 0.11 to 4.64; one RCT, N = 46, very low quality evidence).The quality of the evidence was moderate, the main limitations being lack of blinding in the included trials, inadequate reporting of study methods, and low event and sample sizes in some trials. AUTHORS' CONCLUSIONS: In women identified as poor responders undergoing ART, pre-treatment with DHEA or testosterone may be associated with improved live birth rates. The overall quality of the evidence is moderate. There is insufficient evidence to draw any conclusions about the safety of either androgen. Definitive conclusions regarding the clinical role of either androgen awaits evidence from further well-designed studies.

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.

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.

BACKGROUND: 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. OBJECTIVES: To evaluate the effectiveness and safety of antibiotic administration prior to ET during ART cycles. SEARCH METHODS: 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. SELECTION CRITERIA: Only randomised controlled trials were included. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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). AUTHORS' CONCLUSIONS: 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.

Fibroids in infertility--consensus statement from ACCEPT (Australasian CREI Consensus Expert Panel on Trial evidence).

Fibroid management is surrounded by considerable controversy and uncertainty. This paper summarises the consensus developed by a group of Australasian subspecialists in reproductive endocrinology and infertility (the ACCEPT group) on the evidence concerning the impact and management of fibroids in infertility. The location of a fibroid within the uterus influences its effect on fertility. Subserosal fibroids do not appear to impact on fertility outcomes. Intramural (IM) fibroids may be associated with reduced fertility and an increased miscarriage rate (MR); however, there is insufficient evidence to inform whether myomectomy for IM fibroids improves fertility outcomes. Submucosal fibroids are associated with reduced fertility and an increased MR, and myomectomy for submucosal fibroids appears likely to improve fertility outcomes. The relative effect of multiple or different sized fibroids on fertility outcomes is uncertain, as is the relative usefulness of myomectomy in these situations. It is recommended that fibroids with suspected cavity involvement are defined by magnetic resonance imaging, sonohysterography or hysteroscopy because modalities such as transvaginal ultrasound and hysterosalpingography lack appropriate sensitivity and specificity. Medical management of fibroids delays efforts to conceive and is not recommended for the management of infertility associated with fibroids. Newer treatments such as uterine artery embolisation, radiofrequency ablation, bilateral uterine artery ligation, magnetic resonance-guided focussed ultrasound surgery and fibroid myolysis require further investigation prior to their establishment in the routine management of fibroid-associated infertility.

Miscarriage karyotype and its relationship with maternal body mass index, age, and mode of conception.

This study investigated the association between miscarriage karyotype and body mass index, maternal age, and mode of conception. Miscarriages after IVF and/or intracytoplasmic sperm injection were less frequently aneuploid; advanced maternal age was associated with an increase in aneuploid products of conception; overweight and obese women aged <35 years were less likely to have aneuploid miscarriages than women in a healthy weight range, suggesting alternate mechanisms for miscarriage in this population.