Subfertility Group Research Articles

Factors affecting clinical pregnancy rates after IUI for the treatment of unexplained infertility and mild male subfertility.

The aim of the present retrospective study was to evaluate intrauterine insemination (IUI) clinical experiences and to define the variables for predicting success. The present study was an observational trial performed in a private IVF center on subfertile couples who had applied for treatment between 2002 and 2012, in which the data of 503 IUI cases were retrospectively reviewed. Couples who had been diagnosed with unexplained and mild male subfertility were included. The primary outcome measure was the clinical pregnancy rate in an attempt to form a predictive model for the odds of a clinical pregnancy. Recorded parameters were used to determine the prediction model. Utilizing univariate logistic regression analysis, clinical pregnancy was positively associated with the duration of infertility (OR=1.09, p=0.089), secondary infertility (OR=1.77, p=0.050), and +4 sperm motility after preparation (OR=1.03, p=0.091). Following an adjustment analysis involving a multivariate logistic regression, clinical pregnancy was still found to positively associate with secondary infertility (OR=2.51, p=0.008). IUI success in secondary infertile couples who were in the unexplained infertility and mild male subfertility groups was higher than that in primary infertile couples, and the chances of pregnancy increased as sperm numbers with +4 motility increased. It is difficult to concomitantly evaluate all these parameters and to determine a predictive parameter in IUI independent from other factors.

Relationship between total protein concentration of seminal plasma and sperm characteristics of highly fertile, fertile and subfertile Barki ram semen collected by electroejaculation

The aim of this study was to determine the relationship between total protein concentration (TPC) of seminal plasma (SP) and semen characteristics in rams. A total of 105 ejaculates from 21 Barki rams, of known fertility (9 highly fertile, 9 fertile and 3 subfertile) were collected by electroejaculation (EE) and used in the present study. An aliquot (200μl) from each ejaculate was used for evaluation of semen characteristics (wave motion, motility, viability, sperm morphology, intact-acrosome, sperm concentration and total sperm count per ejaculate). The remaining volume was centrifuged to collect SP and TPC (g/dl) of SP was estimated with hand-held Refractometer; then SP proteins were separated on 15% (w/v) polyacrylamide gel. The results revealed that TPC of SP and almost all semen characteristics were significantly (P<0.05) lower in subfertile (SF) group than both highly fertile (HF) and fertile (F) groups but the longest (85.0±4.1s) stimulation time (ST) was recorded in SF group. Moreover, TPC of SP in HF and F groups showed highly significant (P<0.001) negative correlation with ST but showed highly significant positive correlation with all semen characteristics. However, in SF group neither ST nor semen characteristics showed any significant correlation with TPC of SP. Eosin-nigrosin (EN) stain, hypoosmotic swelling test (HOST) and glutaraldehyde fixation (GF) were capable to discriminate among HF, F and SF groups of rams. In total, fourteen protein bands with different molecular weights, ranging from 7 to 91kDa, were detected on polyacrylamide gel. Protein bands of 11, 13 and 22.5kDa were more prominent in HF group than F group but it was faint to absent in SF group. Moreover, bands of 91, 80 and 27kDa were prominent in F and SF groups than HF group. In conclusion, TPC and protein profile of SP were closely correlated with semen characteristics and might be useful tools to determine ram fertility or semen quality. Protein bands of 11, 13 and 22.5kDa were fertility-associated proteins in Barki rams SP. The effects of these fertility-associated proteins on sperm cell function required further investigation.

Acupuncture for polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) is characterised by the clinical signs of oligo-amenorrhoea, infertility and hirsutism. Conventional treatment of PCOS includes a range of oral pharmacological agents, lifestyle changes and surgical modalities. Beta-endorphin presents in the follicular fluid of both normal and polycystic ovaries. It was demonstrated that the beta-endorphin levels in ovarian follicular fluid of otherwise healthy women who were undergoing ovulation were much higher than the levels measured in plasma.Given that acupuncture has an impact on beta-endorphin production, which may affect gonadotropin-releasing hormone (GnRH) secretion, it is postulated that acupuncture may have a role in ovulation induction and fertility. To assess the effectiveness and safety of acupuncture treatment of oligo/anovulatory women with polycystic ovarian syndrome (PCOS). We identified relevant studies from databases including the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, EMBASE, PsycINFO, CNKI and trial registries. The data are current to 19 October 2015. We included randomised controlled trials (RCTs) that studied the efficacy of acupuncture treatment for oligo/anovulatory women with PCOS. We excluded quasi- or pseudo-RCTs. Primary outcomes were live birth and ovulation (primary outcomes), and secondary outcomes were clinical pregnancy, restoration of menstruation, multiple pregnancy, miscarriage and adverse events. We assessed the quality of the evidence using GRADE methods. Two review authors independently selected the studies, extracted data and assessed risk of bias. We calculated Mantel-Haenszel odds ratios (ORs) and mean difference (MD) and 95% confidence intervals (CIs). We included five RCTs with 413 women. They compared true acupuncture versus sham acupuncture (two RCTs), true acupuncture versus relaxation (one RCT), true acupuncture versus clomiphene (one RCT) and electroacupuncture versus physical exercise (one RCT). Four of the studies were at high risk of bias in at least one domain.No study reported live birth rate. Two studies reported clinical pregnancy and found no evidence of a difference between true acupuncture and sham acupuncture (OR 2.72, 95% CI 0.69 to 10.77, two RCTs, 191 women, very low quality evidence).Three studies reported ovulation. One RCT reported number of women who had three ovulations during three months of treatment but not ovulation rate. One RCT found no evidence of a difference in mean ovulation rate between true and sham acupuncture (MD -0.03, 95% CI -0.14 to 0.08, one RCT, 84 women, very low quality evidence). However, one other RCT reported very low quality evidence to suggest that true acupuncture might be associated with higher ovulation frequency than relaxation (MD 0.35, 95% CI 0.14 to 0.56, one RCT, 28 women).Two studies reported menstrual frequency. One RCT reported true acupuncture reduced days between menstruation more than sham acupuncture (MD 220.35, 95% CI 252.85 to 187.85, 146 women). One RCT reported electroacupuncture increased menstrual frequency more than no intervention (0.37, 95% CI 0.21 to 0.53, 31 women).There was no evidence of a difference between the groups in adverse events. Evidence was very low quality with very wide CIs and very low event rates.Overall evidence was low or very low quality. The main limitations were failure to report important clinical outcomes and very serious imprecision. Thus far, only a limited number of RCTs have been reported. At present, there is insufficient evidence to support the use of acupuncture for treatment of ovulation disorders in women with PCOS.

Recombinant versus urinary human chorionic gonadotrophin for final oocyte maturation triggering in IVF and ICSI cycles.

For the last few decades urinary human chorionic gonadotrophin (uhCG) has been used to trigger final oocyte maturation in cycles of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Recombinant technology has allowed the production of two drugs, recombinant human chorionic gonadotrophin (rhCG) and recombinant luteinising hormone (rLH), that can be used for the same purpose, to mimic the endogenous luteinising hormone (LH) surge. This allows commercial manufacturers to adjust production according to market requirements and to remove all urinary contaminants, facilitating the safe subcutaneous administration of a compound with less batch-to-batch variation. However, prior to a change in practice, it is necessary to compare the effectiveness of the recombinant drugs to the currently used urinary human chorionic gonadotrophin (uhCG). To assess the effects of subcutaneous rhCG and high dose rLH versus uhCG for inducing final oocyte maturation in subfertile women undergoing IVF and ICSI cycles. We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (April 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 3), MEDLINE (1946 to April 2015), EMBASE (1980 to April 2015) and PsycINFO (1806 to April 2015) as well as trial registers at ClinicalTrials.gov on 13 May 2015 and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) search portal on 14 May 2015. Two review authors independently scanned titles and abstracts and selected those that appeared relevant for collection of the full paper. We included randomised controlled trials comparing rhCG and rLH with urinary hCG for final oocyte maturation triggering in IVF and ICSI cycles for treatment of infertility in normogonadotropic women. Two authors independently performed assessment for inclusion or exclusion, quality assessment and data extraction. We discussed any discrepancies in the presence of a third author to reach a consensus. The primary review outcomes were ongoing pregnancy/live birth and incidence of ovarian hyperstimulation syndrome (OHSS). Clinical pregnancy, miscarriage rate, number of oocytes retrieved and adverse events were secondary outcomes. We combined data to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs) and assessed statistical heterogeneity using the I(2) statistic. We evaluated the overall quality of the evidence for the main comparisons using GRADE methods. We included 18 RCTs involving 2952 participants; 15 compared rhCG with uhCG, and 3 compared rhLH with uhCG. The evidence for different comparisons ranged from very low to high quality: limitations were poor reporting of study methods and imprecision. Pharmaceutical companies funded 9 of the 18 studies, and 5 studies did not clearly report funding source. Ongoing pregnancy/live birthThere was no conclusive evidence of a difference between rhCG and uhCG (OR 1.15, 95% CI 0.89 to 1.49; 7 RCTs, N = 1136, I(2) = 0%, moderate quality evidence) or between rhLH and uhCG (OR 0.95, 95% CI 0.51 to 1.78, 2 RCTs, N = 289, I(2) = 0%, very low quality evidence) for ongoing pregnancy/live birth rates. OHSS There was no evidence of a difference between rhCG and uhCG in the incidence of OHSS: moderate to severe OHSS (OR 1.76, 95% CI 0.37 to 8.45; 3 RCTs, N = 417, I(2) = 0%, low quality evidence), moderate OHSS (OR 0.78, 95% CI 0.27 to 2.27; 1 RCT, N = 243, I(2) = 0%, low quality evidence), mild to moderate OHSS (OR 1.00, 95% CI 0.42 to 2.38; 2 RCTs, N = 320, I(2) = 0%, low quality evidence) or undefined OHSS (OR 1.18, 95% CI 0.50 to 2.78; 3 RCTs, N = 495, I(2) = 0%, low quality evidence). Likewise, there was no evidence of a difference between rhLH and uhCG in OHSS rates for moderate OHSS (OR 0.82, 95% CI 0.39 to 1.69, 2 RCTs, N = 280, I(2) = 5%, very low quality evidence). Other adverse events There was no evidence of a difference in miscarriage rates between rhCG and uhCG (OR 0.72, 95% CI 0.41 to 1.25; 8 RCTs, N = 1196, I(2) = 0%, low quality evidence) or between rhLH and uhCG (OR 0.95, 95% CI 0.38 to 2.40; 2 RCTs, N = 289, I(2) = 0%, very low quality evidence). For other adverse effects (most commonly injection-site reactions) rhCG was associated with a lower number of adverse events than uhCG (OR 0.52, 95% CI 0.35 to 0.76; 5 RCTS, N = 561; I(2) = 67%, moderate quality evidence). However, when we used a random-effects model due to substantial statistical heterogeneity, there was no evidence of a difference between the groups (OR 0.56, 95% CI 0.27 to 1.13). Only one study comparing rLH and uhCG reported other adverse events, and it was impossible to draw conclusions. We conclude that there is no evidence of a difference between rhCG or rhLH and uhCG for live birth or ongoing pregnancy rates or rates of OHSS.

Assisted Reproductive Technology and Early Intervention Program Enrollment.

We examined the prevalence of Early Intervention (EI) enrollment in Massachusetts comparing singleton children conceived via assisted reproductive technology (ART), children born to mothers with indicators of subfertility but no ART (Subfertile), and children born to mothers who had no indicators of subfertility and conceived naturally (Fertile). We assessed the natural direct effect (NDE), the natural indirect effect (NIE) through preterm birth, and the total effect of ART and subfertility on EI enrollment. We examined maternal and infant characteristics among singleton ART (n = 6447), Subfertile (n = 5515), and Fertile (n = 306,343) groups and characteristics associated with EI enrollment includingpreterm birth using χ(2) statistics (α = 0.05). We estimated the NDE and NIE of the ART-EI enrollment relationship by fitting a model for enrollment, conditional on ART, preterm and the ART-preterm delivery interaction, and covariates. Similar analyses were conducted by using Subfertile as the exposure. The NDE indicated that the odds of EI enrollment were 27% higher among the ART group (odds ratioNDE = 1.27; 95% confidence interval (CI): 1.19 ̶ 1.36) and 20% higher among the Subfertilegroup (odds ratioNDE = 1.20; 95% CI: 1.12 ̶ 1.29) compared with the Fertile group, even if the rate of preterm birth is held constant. Singleton children conceived through ART and children of subfertile mothers both have elevated risks of EI enrollment. These findings have implications for clinical providers as they counsel women about child health outcomes associated with ART or subfertility.

Acupuncture for treating polycystic ovary syndrome: guidance for future randomized controlled trials.

To provide guidance for future randomized controlled trials (RCTs) based on a review concerning acupuncture for treating polycystic ovary syndrome (PCOS). A comprehensive literature search was conducted in October 2015 using MEDLINE, EMBASE, SCISEARCH, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Menstrual Disorders and Subfertility Group trials register, Allied and Complementary Medicine (AMED), China National Knowledge Infrastructure (CNKI), and the Wanfang databases. RCTs comparing either acupuncture with no/sham/pharmacological intervention or a combination of acupuncture and conventional therapy with conventional therapy in the treatment of PCOS were included in this review. A quality evaluation was performed for each of the included studies. Thirty-one RCTs were included in the review and were divided into four categories according to the type of intervention used in the comparator or control group. Menstrual frequency, hormones, anthropometrics, insulin sensitivity, blood lipids, and fertility were used as the main measurements to assess the effects of acupuncture on the patients with PCOS. Thirty trials, except for one, showed an improvement in at least one of the indicators of PCOS after acupuncture treatment. However, normalizing the methodological and reporting format remains an issue. Based upon this review of current clinical trials concerning acupuncture for treating PCOS, we provide guidelines for better clinical trial design in the future.

Assisted reproductive technologies for male subfertility.

Intra-uterine insemination (IUI), in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) are frequently used fertility treatments for couples with male subfertility. The use of these treatments has been subject of discussion. Knowledge on the effectiveness of fertility treatments for male subfertility with different grades of severity is limited. Possibly, couples are exposed to unnecessary or ineffective treatments on a large scale. To evaluate the effectiveness and safety of different fertility treatments (expectant management, timed intercourse (TI), IUI, IVF and ICSI) for couples whose subfertility appears to be due to abnormal sperm parameters. We searched for all publications that described randomised controlled trials (RCTs) of the treatment for male subfertility. We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO and the National Research Register from inception to 14 April 2015, and web-based trial registers from January 1985 to April 2015. We applied no language restrictions. We checked all references in the identified trials and background papers and contacted authors to identify relevant published and unpublished data. We included RCTs comparing different treatment options for male subfertility. These were expectant management, TI (with or without ovarian hyperstimulation (OH)), IUI (with or without OH), IVF and ICSI. We included only couples with abnormal sperm parameters. Two review authors independently selected the studies, extracted data and assessed risk of bias. They resolved disagreements by discussion with the rest of the review authors. We performed statistical analyses in accordance with the guidelines for statistical analysis developed by The Cochrane Collaboration. The quality of the evidence was rated using the GRADE methods. Primary outcomes were live birth and ovarian hyperstimulation syndrome (OHSS) per couple randomised. The review included 10 RCTs (757 couples). The quality of the evidence was low or very low for all comparisons. The main limitations in the evidence were failure to describe study methods, serious imprecision and inconsistency. IUI versus TI (five RCTs)Two RCTs compared IUI with TI in natural cycles. There were no data on live birth or OHSS. We found no evidence of a difference in pregnancy rates (2 RCTs, 62 couples: odds ratio (OR) 4.57, 95% confidence interval (CI) 0.21 to 102, very low quality evidence; there were no events in one of the studies).Three RCTs compared IUI with TI both in cycles with OH. We found no evidence of a difference in live birth rates (1 RCT, 81 couples: OR 0.89, 95% CI 0.30 to 2.59; low quality evidence) or pregnancy rates (3 RCTs, 202 couples: OR 1.51, 95% CI 0.74 to 3.07; I(2) = 11%, very low quality evidence). One RCT reported data on OHSS. None of the 62 women had OHSS.One RCT compared IUI in cycles with OH with TI in natural cycles. We found no evidence of a difference in live birth rates (1 RCT, 44 couples: OR 3.14, 95% CI 0.12 to 81.35; very low quality evidence). Data on OHSS were not available. IUI in cycles with OH versus IUI in natural cycles (five RCTs)We found no evidence of a difference in live birth rates (3 RCTs, 346 couples: OR 1.34, 95% CI 0.77 to 2.33; I(2) = 0%, very low quality evidence) and pregnancy rates (4 RCTs, 399 couples: OR 1.68, 95% CI 1.00 to 2.82; I(2) = 0%, very low quality evidence). There were no data on OHSS. IVF versus IUI in natural cycles or cycles with OH (two RCTs)We found no evidence of a difference in live birth rates between IVF versus IUI in natural cycles (1 RCT, 53 couples: OR 0.77, 95% CI 0.25 to 2.35; low quality evidence) or IVF versus IUI in cycles with OH (2 RCTs, 86 couples: OR 1.03, 95% CI 0.43 to 2.45; I(2) = 0%, very low quality evidence). One RCT reported data on OHSS. None of the women had OHSS.Overall, we found no evidence of a difference between any of the groups in rates of live birth, pregnancy or adverse events (multiple pregnancy, miscarriage). However, most of the evidence was very low quality.There were no studies on IUI in natural cycles versus TI in stimulated cycles, IVF versus TI, ICSI versus TI, ICSI versus IUI (with OH) or ICSI versus IVF. We found insufficient evidence to determine whether there was any difference in safety and effectiveness between different treatments for male subfertility. More research is needed.

Intra-uterine insemination for unexplained subfertility.

Background Intra-uterine insemination (IUI) is a widely used fertility treatment for couples with unexplained subfertility. Although IUI is less invasive and less expensive than in vitro fertilisation (IVF), the safety of IUI in combination with ovarian hyperstimulation (OH) is debated. The main concern about IUI treatment with OH is the increase in multiple pregnancy rates. Objectives To determine whether for couples with unexplained subfertility IUI improves the live birth rate compared with timed intercourse (TI), both with and without ovarian hyperstimulation. Search strategy We searched the Cochrane Menstrual Disorder and Subfertility Group Trials Register ( searched March 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2005, Issue 4), MEDLINE (1966 to November 2005), EMBASE (1980 to November 2005), SCIsearch and reference lists of articles. Authors of identified studies were contacted for missing or unpublished data. Selection criteria Truly randomised controlled trials (RCTs) with at least one of the following comparisons were included: - IUI versus TI, both in a natural cycle; - IUI versus TI, both in a stimulated cycle; - IUI in a natural cycle versus IUI in a stimulated cycle; - IUI with OH versus TI in natural cycle; - IUI in a natural cycle versus TI with OH. Only couples with unexplained subfertility were included. Data collection and analysis Quality assessment and data extraction were performed independently by two review authors. Outcomes were extracted and the data were pooled. Subgroup analyses and sensitivity analyses were done where possible. Main results In the six trials where IUI was compared with TI, both in stimulated cycles, there was evidence of an increased chance of pregnancy (six RCTs, 517 women: OR 1.68, 95% CI 1.13 to 2.50). A significant increase in pregnancy rate was also found for women where IUI with OH was compared with IUI in a natural cycle (three RCTs, 415 women: OR 2.33, 95% CI 1.46 to 3.71). However, the trials provided insufficient data to investigate the impact of IUI with or without OH on several important outcomes including live birth, multiple pregnancies, miscarriage and risk of ovarian hyperstimulation. There was no evidence of a difference in pregnancy rate for IUI with OH compared with TI in a natural cycle (one RCT, 51 women: OR 4.05, 95% CI 0.39 to 41.87). No RCTs were found for the other two comparisons. Authors' conclusions There is evidence that IUI with OH increases the live birth rate compared to IUI alone. The likelihood of pregnancy was also increased for treatment with IUI compared to TI both in stimulated cycles. There is insufficient data on multiple pregnancies and other adverse events for treatment with OH. Therefore, couples should be fully informed about the risks of IUI and OH as well as alternative treatment options.

The impact of sperm morphology on the outcome of intrauterine insemination cycles with gonadotropins in unexplained and male subfertility

ObjectiveTo determine the impact of sperm morphology on success of intrauterine insemination (IUI) in unexplained and male subfertility. Study designBasal and post-wash normal percentage of sperm with normal morphology was assessed prospectively in 412 couples with 530 IUI cycles who underwent ovarian hyperstimulation with gonadotropins. The primary outcome was live birth per cycle. Receiver operating characteristics (ROC) curves were used to determine the effectiveness of sperm morphology to predict live birth in IUI cycles. ResultsNormal sperm morphology (%) after preparation was higher in patients with live birth (5.4±4.5 vs 4.3±4.1; respectively, p<.05) in study population. In male subfertile group, normal sperm morphology before and after sperm preparation was higher in patients with live birth (1.3±1.4 vs 0.6±0.9; p<0.001 and 4.6±4.4 vs 1.9±2.2; p<0.01, respectively). However, both basal and post-wash normal sperm morphology (%) were similar in patients with and without live birth in unexplained group. The best cut-off value for normal sperm morphology (%) to predict live birth was 4.5% in male subfertile group with a sensitivity of 50.6% and specificity of 61.7%. ConclusionMorphological evaluation is not a reliable parameter alone for predicting pregnancy outcome in unexplained infertility. In male subfertility, post-wash normal sperm morphology percentage higher than 4.5 increases the probability of live birth.

Trocar types in laparoscopy.

Laparoscopic surgery has led to great clinical improvements in many fields of surgery; however, it requires the use of trocars, which may lead to complications as well as postoperative pain. The complications include intra-abdominal vascular and visceral injury, trocar site bleeding, herniation and infection. Many of these are extremely rare, such as vascular and visceral injury, but may be life-threatening; therefore, it is important to determine how these types of complications may be prevented. It is hypothesised that trocar-related complications and pain may be attributable to certain types of trocars. This systematic review was designed to improve patient safety by determining which, if any, specific trocar types are less likely to result in complications and postoperative pain. To analyse the rates of trocar-related complications and postoperative pain for different trocar types used in people undergoing laparoscopy, regardless of the condition. Two experienced librarians conducted a comprehensive search for randomised controlled trials (RCTs) in the Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, CDSR and DARE (up to 26 May 2015). We checked trial registers and reference lists from trial and review articles, and approached content experts. RCTs that compared rates of trocar-related complications and postoperative pain for different trocar types used in people undergoing laparoscopy. The primary outcomes were major trocar-related complications, such as mortality, conversion due to any trocar-related adverse event, visceral injury, vascular injury and other injuries that required intensive care unit (ICU) management or a subsequent surgical, endoscopic or radiological intervention. Secondary outcomes were minor trocar-related complications and postoperative pain. We excluded trials that studied non-conventional laparoscopic incisions. Two review authors independently conducted the study selection, risk of bias assessment and data extraction. We used GRADE to assess the overall quality of the evidence. We performed sensitivity analyses and investigation of heterogeneity, where possible. We included seven RCTs (654 participants). One RCT studied four different trocar types, while the remaining six RCTs studied two different types. The following trocar types were examined: radially expanding versus cutting (six studies; 604 participants), conical blunt-tipped versus cutting (two studies; 72 participants), radially expanding versus conical blunt-tipped (one study; 28 participants) and single-bladed versus pyramidal-bladed (one study; 28 participants). The evidence was very low quality: limitations were insufficient power, very serious imprecision and incomplete outcome data. Primary outcomesFour of the included studies reported on visceral and vascular injury (571 participants), which are two of our primary outcomes. These RCTs examined 473 participants where radially expanding versus cutting trocars were used. We found no evidence of a difference in the incidence of visceral (Peto odds ratio (OR) 0.95, 95% confidence interval (CI) 0.06 to 15.32) and vascular injury (Peto OR 0.14, 95% CI 0.0 to 7.16), both very low quality evidence. However, the incidence of these types of injuries were extremely low (i.e. two cases of visceral and one case of vascular injury for all of the included studies). There were no cases of either visceral or vascular injury for any of the other trocar type comparisons. No studies reported on any other primary outcomes, such as mortality, conversion to laparotomy, intensive care admission or any re-intervention. Secondary outcomesFor trocar site bleeding, the use of radially expanding trocars was associated with a lower risk of trocar site bleeding compared to cutting trocars (Peto OR 0.28, 95% CI 0.14 to 0.54, five studies, 553 participants, very low quality evidence). This suggests that if the risk of trocar site bleeding with the use of cutting trocars is assumed to be 11.5%, the risk with the use of radially expanding trocars would be 3.5%. There was insufficient evidence to reach a conclusion regarding other trocar types, their related complications and postoperative pain, as no studies reported data suitable for analysis. Data were lacking on the incidence of major trocar-related complications, such as visceral or vascular injury, when comparing different trocar types with one another. However, caution is urged when interpreting these results because the incidence of serious complications following the use of a trocar was extremely low. There was very low quality evidence for minor trocar-related complications suggesting that the use of radially expanding trocars compared to cutting trocars leads to reduced incidence of trocar site bleeding. These secondary outcomes are viewed to be of less clinical importance.Large, well-conducted observational studies are necessary to answer the questions addressed in this review because serious complications, such as visceral or vascular injury, are extremely rare. However, for other outcomes, such as trocar site herniation, bleeding or infection, large observational studies may be needed as well. In order to answer these questions, it is advisable to establish an international network for recording these types of complications following laparoscopic surgery.

Vitamin D deficiency among subfertile women: case-control study

Objective: The objective of the study is to compare the dietary vitamin D and calcium intake among subfertile women (cases) versus pregnant women (controls) and to determine the vitamin D levels in the subfertile and pregnant women. The study design was an observational case-control study where a total of 181 (83 previously diagnosed subfertile cases from various causes and 98 pregnant controls) women of reproductive age. A validated questionnaire was used where it focused on key indicators evaluating vitamin D-related factors. Blood was withdrawn for the measurement of serum calcium, albumin and phosphate to exclude secondary causes that might affect vitamin D level.Results: The prevalence of vitamin D deficiency was significantly higher in the subfertile group than controls (59.0% versus 40.4%; p < 0.01). Calcium supplements intake was significantly higher in controls than the subfertile group (64.6% versus 10.0%; p value < 0.001). Total dietary vitamin D intake (> 400 IU/day) was significantly higher in the controls than the subfertile group.Conclusion: Vitamin D deficiency is prevalent among subfertile women. Optimization of serum calcium and vitamin D levels is encouraged.

Oral Zinc Supplementation Restores Superoxide Radical Scavengers to Normal Levels in Spermatozoa of Iraqi Asthenospermic Patients

Oxidative stress and decreased antioxidant levels have been projected as potential factors involved in the pathophysiology of diverse male infertility types, including asthenospermia. The present study was conducted to examine the effect of zinc supplementation on the quantitative and qualitative characteristics of semen along with oxido-sensitive index level (superoxide dismutase/xanthine oxidase ratio) in the seminal plasma of asthenospermic patients. Semen samples were obtained from 60 fertile (age 31.6 ± 3.3 years) and 60 asthenospermic men (age 32.5 ± 3.23 years) from July 2011 to July 2012, from couples who had consulted the infertility clinic of the Babil hospital of maternity (Hillah, Iraq). The subfertile group was treated with zinc sulfate, every participant took 2 capsules (220 mg each) of zinc sulfate per day for 3 months. Semen samples were obtained (before and after zinc sulfate supplementation). Oxido-sensitive index level, catalase-like activity and various sperm parameters were measured. The value of the oxido-sensitive index of fertile controls (1.28 + 0.31 in seminal plasma and 1.57 + 0.62 in spermatozoa) was significantly higher than that of the infertile patient group (0.56 + 0.48 in seminal plasma and 0.65 + 0.57 spermatozoa) (p = 0.0001). Oxido-sensitive index levels were significantly higher in the infertile group treated with zinc sulfate (1.13 + 0.22 in seminal plasma and 1.15 + 0.16 in spermatozoa) (p = 0.001). Catalase-like activity was increased significantly in spermatozoa and seminal plasma of patients compared to that of healthy controls. Volume of semen, progressive sperm motility and total normal sperm count were increased after zinc supplementation. Zinc supplementation restores oxido-sensitive index and catalase-like activity in semen of asthenozoospermic subjects to normal ranges.

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

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

Culture media for human pre-implantation embryos in assisted reproductive technology cycles.

Many media are commercially available for culturing pre-implantation human embryos in assisted reproductive technology (ART) cycles. It is unknown which culture medium leads to the best success rates after ART. To evaluate the safety and effectiveness of different human pre-implantation embryo culture media in used for in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) cycles. We searched the Cochrane Menstrual Disorders and Subfertility Group's Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the National Research Register, the Medical Research Council's Clinical Trials Register and the NHS Center for Reviews and Dissemination databases from January 1985 to March 2015. We also examined the reference lists of all known primary studies, review articles, citation lists of relevant publications and abstracts of major scientific meetings. We included all randomised controlled trials which randomised women, oocytes or embryos and compared any two commercially available culture media for human pre-implantation embryos in an IVF or ICSI programme. Two review authors independently selected the studies, assessed their risk of bias and extracted data. We sought additional information from the authors if necessary. We assessed the quality of the evidence using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methods. The primary review outcome was live birth or ongoing pregnancy. We included 32 studies in this review. Seventeen studies randomised women (total 3666), three randomised cycles (total 1018) and twelve randomised oocytes (over 15,230). It was not possible to pool any of the data because each study compared different culture media.Only seven studies reported live birth or ongoing pregnancy. Four of these studies found no evidence of a difference between the media compared, for either day three or day five embryo transfer. The data from the fifth study did not appear reliable.Six studies reported clinical pregnancy rate. One of these found a difference between the media compared, suggesting that for cleavage-stage embryo transfer, Quinn's Advantage was associated with higher clinical pregnancy rates than G5 (odds ratio (OR) 1.56; 95% confidence interval (CI) 1.12 to 2.16; 692 women). This study was available only as an abstract and the quality of the evidence was low.With regards to adverse effects, three studies reported multiple pregnancies and six studies reported miscarriage. None of them found any evidence of a difference between the culture media used. None of the studies reported on the health of offspring.Most studies (22/32) failed to report their source of funding and none described their methodology in adequate detail. The overall quality of the evidence was rated as very low for nearly all comparisons, the main limitations being imprecision and poor reporting of study methods. An optimal embryo culture medium is important for embryonic development and subsequently the success of IVF or ICSI treatment. There has been much controversy about the most appropriate embryo culture medium. Numerous studies have been performed, but no two studies compared the same culture media and none of them found any evidence of a difference between the culture media used. We conclude that there is insufficient evidence to support or refute the use of any specific culture medium. Properly designed and executed randomised trials are necessary.

In vitro fertilisation for unexplained subfertility.

In vitro fertilisation for unexplained subfertility.

Gonadotrophin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction.

Gonadotrophin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction.

Knowledge regarding subfertility among patients who are attending to general surgical and subfertility clinics at the Teaching Hospital Peradeniya

Background Subfertility is a common medical condition which can lead to many social and psychological problems. Good knowledge regarding subfertility may help to decrease the incidence of infertility by allowing couples to avoid certain risk factors and it will facilitate the management. The aim of our study was to assess knowledge regarding subfertility among Sri Lankans. Method A cross-sectional study was conducted with a total of 426 subjects including 158 fertile participants, 138 unmarried participants from general surgical clinics and 130 subfertile patients from the subfertility clinic at the teaching hospital Peradeniya. Study was conducted using a self administered questionnaire during May, June and July 2015. Results Generally a poor level of knowledge (44.71%) was reported by participants. Knowledge was significantly higher in subfertile group (48.93%) compared to fertile (42.32%, P=0.006) and unmarried (43.47%, P=0.035) groups. Only 29.81% of total population knows when to seek medical advices for subfertility, with no significant difference between groups (fertile-30.4%, subfertile-28.5%, unmarried-30.4%). Though 69.73% of total population (60.1% of fertile, 89.2% of subfertile, 60.9% of unmarried) correctly recommended a Gynaecologist for first consultation, only 8.23% of total (7% of fertile, 4.6% of subfertile, 13% of unmarried) correctly selected Andrologist for male fertility problems. Conclusions These findings suggest poor knowledge regarding subfertility, particularly regarding male subfertility which is far less than knowledge regarding female subfertility. In general, subfertile patients have a significantly higher level of knowledge than fertile and unmarried patients, but regarding some specific points all three groups have a low level of knowledge.

Biochemical markers of placental dysfunction in assisted conception

A possible mechanism for poor perinatal outcomes in singleton pregnancies conceived following assisted reproductive technologies (ART) and those conceived naturally following a period of infertility (>12 months) is thought to be placental dysfunction. This was investigated by measuring plasma concentrations of biochemical markers: (i) soluble fms-like tyrosine kinase1 (sFlt1); (ii) placental growth factor (PlGF); (iii) leptin; and (iv) plasminogen activator inhibitor 2 (PAI-2), serially at four antenatal time points. Baseline concentrations of each marker after delivery were also measured. The control group was naturally conceived singleton pregnancies with no history of infertility. Non-smoking, age-matched nulliparous women with no significant medical history were recruited to all groups. The ART group had significantly lower mean plasma concentrations of PlGF at all antenatal time points compared to the control group (p < 0.001). The subfertility (SF) group had significantly higher mean serum concentrations of leptin than the other groups at all time points (p < 0.001), even after correction for body mass index. There were no significant differences in sFlt1 and PAI-2 concentrations between the groups. Low plasma PlGF concentrations in the ART group might suggest abnormal placentation and/or abnormal function in ART pregnancies with relevance to pathogenesis of pregnancy complications in these women.

Pain relief in hysterosalpingography.

Background Hysterosalpingography (HSG) is a method of testing for tubal patency. Various pharmacological strategies are available that may reduce the pain during the procedure. Objectives To compare the effectiveness of different types of pharmacological interventions for pain relief in women undergoing hysterosalpingography (HSG) for investigation of subfertility. Search methods This review has drawn on the search strategy developed for the Menstrual Disorders and Subfertility Group. In addition MEDLINE and EMBASE were searched up to July 2006. Selection criteria All randomised controlled trials investigating the pharmacological interventions for pain relief during HSG were investigated. Data collection and analysis Data were extracted independently by the first two authors. Differences of opinion were registered and resolved by the third author. Results for each study were expressed as mean pain score and standard error of the mean with 95% confidence intervals. Main results The included eight trials reported on 570 women undergoing HSG. Overall, there was no evidence of benefit of using any analgesia compared with placebo for pain relief during the procedure (standard mean difference (SMD) of -0.05 (95%CI -0.25 to 0.14) or up to 29 minutes after HSG SMD 0.17, (95%CI -1.00 to 1.34)). Four RCTs involving 219 women found evidence of benefit with any analgesia in comparison to placebo for pain relief more than 30 minutes after HSG, with the SMD of -0.82(95%CI-1.18 to -0.45). One RCT involving 91 women compared the effectiveness of opioid analgesics versus non-opioid analgesics and reported no evidence of difference in pain relief at any stage of the procedure. One RCT involving 20 women compared the use of topical analgesia with a paracervical block, with analysis demonstrating more benefit to be gained from using topical analgesia during HSG, with the SMD of -2.03 (95%Cl-3.16 to -0.91). Authors' conclusions There is little evidence of benefit in terms of pain relief of any of the interventions considered in this study during or immediately after HSG. However, there is limited evidence of pain reduction 30 minutes after the procedure. Further RCTs should consider the role of non steroidal antiinflammatories (NSAIDs) and intrauterine anaesthetic during HSG.

Gonadotrophins for ovulation induction in women with polycystic ovarian syndrome.

Ovulation induction with follicle stimulating hormone (FSH) is the second-line treatment in women with polycystic ovary syndrome (PCOS) who do not ovulate or conceive on clomiphene citrate (CC). To compare the effectiveness and safety of gonadotrophins as a second-line treatment for ovulation induction in women with CC-resistant PCOS. We searched the Menstrual Disorders & Subfertility Group's Specialist Register of controlled trials, the Cochrane Central Register of Controlled Trials, MEDLINE (1966 to October 2014), EMBASE (1980 to October 2014), CINAHL (1982 to October 2014), National Research Register and web-based trials databases such as Current Controlled Trials. There was no language restriction. All randomised controlled trials reporting data on comparing clinical outcomes in women with PCOS who did not ovulate or conceive on CC, and undergoing ovulation induction with urinary FSH (uFSH: FSH-P or FSH-HP), HMG/HP-HMG or recombinant FSH. We included trials reporting on ovulation induction followed by intercourse or intrauterine insemination. We excluded studies that used co-treatment with CC, metformin, LH or letrozole. Three review authors (NW, MN and MvW) independently selected studies for inclusion, assessed study quality and extracted study data. Primary outcomes were live birth rate per woman (effectiveness outcome) and incidence of ovarian hyperstimulation syndrome (OHSS) per woman (safety outcome). Secondary outcomes were clinical pregnancy, miscarriage, multiple pregnancy, total gonadotrophin dose and total duration of stimulation per woman. We combined data using a fixed-effect model to calculate the odds ratio (OR). We summarised the overall quality of evidence for the main outcomes using GRADE criteria. The review includes 14 trials with 1726 women. Ten trials compared rFSH versus urinary-derived gonadotrophins (three rFSH versus HMG and seven rFSH versus FSH-HP), four trials compared FSH-P with HMG. We found no trials that compared FSH-HP with FSH-P.We found no evidence of a difference in live birth for rFSH versus urinary-derived gonadotrophins (OR 1.26, 95% CI 0.80 to 1.99, 5 trials, 505 women, I² = 0%, low-quality evidence) or clinical pregnancy rate (OR 1.08, 95% CI 0.83 to 1.39, 8 trials, 1330 women, I² = 0, low-quality evidence). This suggests that for the observed average live birth per woman with urinary-derived FSH of 16%, the chance of live birth following rFSH is between 13% and 26%.For the comparison HMG or HP-HMG versus FSH-P there was also no difference in the evidence on live birth rate (OR 1.36, 95% CI 0.58 to 3.18, 3 trials, 138 women, I² = 0%, low-quality evidence). This suggests that for a woman with a live birth rate of 18% with HMG or HP-HMG, the chance of live birth following uFSH is between 9% and 37%.Trial authors used various definitions for OHSS. Pooling the data, we found no evidence of a difference for rFSH versus urinary-derived gonadotrophins (OR 1.52, 95% CI 0.81 to 2.84, 10 trials, 1565 women, I(2) = 0%, very low-quality evidence) and for HMG or HP-HMG versus FSH-P (OR 9.95, 95% CI 0.47 to 210.19, 2 trials, 53 women, I² = 0%, very low-quality evidence). In women with PCOS and CC resistance or CC failure, we found no evidence of a difference in live birth and OHSS rates between urinary-derived gonadotrophins and rFSH or HMG/HP-HMG. Evidence for all outcomes was of low or very low quality. We suggest weighing costs and convenience in the decision to use one or the other.