Live Birth Rate Outcomes Research Articles

O-020 Investigating the effect of advanced sperm preparation techniques on embryo developmental potential and clinical outcomes: a network meta-analysis of randomized controlled trials

Abstract Study question Are embryological and clinical outcomes affected when employing Magnetic-Activated Cell-Sorting (MACS), Density Gradient Centrifuge (DGC)-Zeta and Microfluidic Sperm Selection (MSS) instead of DGC and Swim-Up? Summary answer MACS and MSS enhance both laboratory and clinical outcomes, while DGC-Zeta seems to improve only clinical outcomes, in comparison to conventional sperm preparation techniques. What is known already Sperm preparation techniques have been developed to enhance sperm selection process towards improving IVF laboratory and clinical outcomes. Based on centrifugation and sperm migration, DGC and swim-up constitute the standard methods for improving sperm parameters, nonetheless disregarding molecular aspects. Certain techniques, namely MACS, DCG/Zeta and MSS have been proposed to effectively select non-apoptotic sperm with intact chromatin and high DNA integrity claiming their place in routine clinical practice. Concurring on the efficacy of these adjunct methods from the standpoint of embryo developmental dynamic and clinical outcomes is both pertinent and imperative. Study design, size, duration A systematic search of the literature was performed in the database Pubmed/Medline up to December 2023. Only full-text manuscripts published in English where randomization was performed on oocytes or patients were eligible. Studies reporting on semen samples obtained by surgical techniques were excluded. A total of 20 RCTs were included in this network meta-analysis. Other reported sperm preparation techniques were excluded due to the limited number of available Randomized Controlled Trials (RCTs). Participants/materials, setting, methods All RCTs providing results on the aforementioned sperm preparation techniques were included. The outcome measures were fertilization, cleavage, blastocyst formation, clinical pregnancy, and live-birth rates. To evaluate the network estimate both direct and indirect effects were assessed. When heterogeneity was I2=0% the fixed-effects model was preferred. In any other case the random-effects model was employed. To rank the sperm preparation techniques' efficiency, the frequentist method employing the P-score was opted for. Main results and the role of chance The 20 included RCTs presented with a total of 17 different designs and 8 different combinations of sperm preparation techniques. Seventeen studies reported on fertilization rate providing no statistically significant difference between the sperm preparation techniques albeit with high heterogeneity I2=69%. Regarding cleavage rate (n = 10 studies), only MACS/DGC presented with an improved outcome when compared to DGC (RR: 1.43; 95%CI: 1.16-1.76; I2=96%). MACS/DGC presented with the highest efficiency (P-Score=0.90), followed by combination of MACS/DGC/swim-up (P-Score=0.83). Both MSS and MACS/DGC presented with significantly higher blastocyst formation rate compared to DGC (MSS: RR:1.14;95%CI:1.02-1.29; MACS: RR: 1.37; 95%CI: 1.04-1.82; I2=0%). According to P-Score, MACS/DGC was presented as the most efficient technique (P-Score=0.89) followed by MSS (P-Score=0.44). Regarding clinical pregnancy rates, the 12 studies featured low heterogeneity (I2=0). MACS/DGC presented with higher clinical pregnancy rates compared to DGC (RR: 1.30; 95%CI: 1.09-1.36) and the combination of DGC/swim-up (RR: 1.55; 95%CI: 1.12-1.95). MSS presented with enhanced results compared to swim-up (RR: 1.37; 95%CI: 1.11-1.69) and DGC-Zeta presented with higher clinical pregnancy rates compared to DGC (RR: 1.76; 95%CI: 1.28-1.92). The most efficient technique was DGC-Zeta (P-Score=0.98), followed by MACS/DGC (P-Score=0.82). Regarding live-birth rates no statistically significant difference was observed, albeit high heterogeneity was observed (I2=51%). Limitations, reasons for caution The blastocyst formation rate and the live-birth rate outcomes should be interpreted with caution due to the limited number of RCTs. The indirect effect estimates may pose as an intrinsic limitation of the network meta-analysis, especially in cases with limited direct data. Wider implications of the findings This data demonstrates that the combination of MACS/DGC provided enhanced laboratory and clinical outcomes compared to conventional techniques. Investigating sperm selection techniques that assess advanced sperm characteristics rather than parameters alone is timely and essential. To concur on optimal practice further RCTs directly comparing MSS, MACS and DGC-Zeta are required. Trial registration number Not applicable

Systematic review and meta-analysis: does pre-implantation genetic testing for aneuploidy at the blastocyst stage improve live birth rate?

PurposeTo establish if preimplantation genetic testing for aneuploidy (PGT-A) at the blastocyst stage improves the composite outcome of live birth rate and ongoing pregnancy rate per embryo transfer compared to conventional morphological assessment.MethodsA systematic literature search was conducted using PubMed, EMBASE and Cochrane database from 1st March 2000 until 1st March 2022. Studies comparing reproductive outcomes following in vitro fertilisation using comprehensive chromosome screening (CCS) at the blastocyst stage with traditional morphological methods were evaluated.ResultsOf the 1307 citations identified, six randomised control trials (RCTs) and ten cohort studies fulfilled the inclusion criteria. The pooled data identified a benefit between PGT-A and control groups in the composite outcome of live birth rate and ongoing pregnancy per embryo transfer in both the RCT (RR 1.09, 95% CI 1.02–1.16) and cohort studies (RR 1.50, 95% CI 1.28–1.76). Euploid embryos identified by CCS were more likely to be successfully implanted amongst the RCT (RR 1.20, 95% CI 1.10–1.31) and cohort (RR 1.69, 95% CI 1.29–2.21) studies. The rate of miscarriage per clinical pregnancy is also significantly lower when CCS is implemented (RCT: RR 0.73, 95% CI 0.56–0.96 and cohort: RR 0.48, 95% CI 0.32–0.72).ConclusionsCCS-based PGT-A at the blastocyst biopsy stage increases the composite outcome of live births and ongoing pregnancies per embryo transfer and reduces the rate of miscarriage compared to morphological assessment alone. In view of the limited number of studies included and the variation in methodology between studies, future reviews and analyses are required to confirm these findings.

MP43-14 THE IMPACT OF VARICOCELE EMBOLISATION ON SPERM DNA FRAGMENTATION & ASSISTED REPRODUCTIVE TECHNOLOGY (ART) OUTCOMES

You have accessJournal of UrologyCME1 Apr 2023MP43-14 THE IMPACT OF VARICOCELE EMBOLISATION ON SPERM DNA FRAGMENTATION & ASSISTED REPRODUCTIVE TECHNOLOGY (ART) OUTCOMES Adwoa Nyantakyi, Sheena Lewis, Yau Thum, Timothy Bracewell-Milnes, James Nicopoullos, Mohamed Al-Hussini, Jonathan Ramsay, Suks Minhas, and Tet Yap Adwoa NyantakyiAdwoa Nyantakyi More articles by this author , Sheena LewisSheena Lewis More articles by this author , Yau ThumYau Thum More articles by this author , Timothy Bracewell-MilnesTimothy Bracewell-Milnes More articles by this author , James NicopoullosJames Nicopoullos More articles by this author , Mohamed Al-HussiniMohamed Al-Hussini More articles by this author , Jonathan RamsayJonathan Ramsay More articles by this author , Suks MinhasSuks Minhas More articles by this author , and Tet YapTet Yap More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003289.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: A varicocele is a common and treatable cause of male infertility. Current guidelines advocate for treatment of varicoceles based on abnormal semenalysis rather than abnormal sperm DNA fragmentation (SDF). High SDF has been associated with poor pregnancy outcomes following ART. The aim of the study was to determine the outcomes of varicocele embolisation in an infertile male population on SDF and subsequent ART outcomes. METHODS: A retrospective study of 130 consecutive male partners of infertile couples with a clinical varicocele between 2015 and 2022 were included. 119 of these men underwent varicocele embolisation by a team of 2 radiologists, whilst 11 declined. SDF was assessed by the alkaline Comet test pre-intervention and at least 3 months after. 84 treated and the 11 untreated men proceeded to ICSI. Baseline couple parameters such as age, and pregnancy and live birth rate outcomes in the ART cycle following this intervention between groups were analysed. T & chi-square tests were used on continuous and categorical data respectively (significance rate p<0.01). RESULTS: Varicocele embolisation significantly reduced the proportion of sperm with DNA damage across all three Comet parameters (p<0.01) (Table 1). Only 18% of these men had normal semenalysis. Baseline parameters for men and women were similar with an average male age of 39 and female age of 37 for both groups. Couples who underwent embolisation had a significantly better pregnancy rate (65% vs 18%, p<0.01) and higher live birth rate which did not reach significance due to low numbers (32% vs 9%, p=0.11). CONCLUSIONS: There was a significant reduction in SDF following varicocele embolisation in this population of men of couples with infertility, with a significant difference in pregnancy rate outcomes in the treated group. Repair of clinical varicoceles improves sperm DNA quality, and can optimize fertility treatment success, even in patient with normal semenalysis. Limitations of the study include small numbers in the ‘untreated’ arm and lack of randomisation, a future avenue for research. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e606 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Adwoa Nyantakyi More articles by this author Sheena Lewis More articles by this author Yau Thum More articles by this author Timothy Bracewell-Milnes More articles by this author James Nicopoullos More articles by this author Mohamed Al-Hussini More articles by this author Jonathan Ramsay More articles by this author Suks Minhas More articles by this author Tet Yap More articles by this author Expand All Advertisement PDF downloadLoading ...

Comparison of pregnancy outcomes of cervical mucus washing with physiologic saline solution or G-Rinse medium solution, in elective single-embryo transfers.

To compare the pregnancy outcomes between physiologic saline and G-Rinse medium solution for cervical mucus washing, in fresh elective single-embryo transfers (ET) in women under the age of 37. This was a retrospective data analysis performed in a single in vitro fertilization (IVF) center between February 2018 and November 2021. Women younger than 37years who underwent single elective ET were included and all women had anti-Mullerian hormone (AMH) levels ≥ 1.5ng/ml. Age, body mass index (BMI), AMH levels, and pregnancy outcomes as clinical pregnancy rate (CPR) and live birth rate (LBR) were analyzed. Study population consisted of 75 women in the G-Rinse medium solution group and 97 women in the physiologic saline group. Clinical pregnancy rate was 58.7% and 61.9% in the G-Rinse medium solution group and saline group, respectively (p = 0.673), and LBR was calculated as 41.3% and 47.4% in the G-Rinse medium solution group and saline group, respectively (p = 0.430). A log-binomial regression model was used and the model was adjusted for BMI to evaluate the effect of the cervical mucus washing method on the pregnancy outcomes. There was an estimated 5% decrease in the relative risk for CPR in the G-Rinse medium solution group compared to the saline group (95% CI: 0.74 to 1.2, p = 0.673). There was an estimated 13% reduction in the relative risk for LBR in the G-Rinse medium solution group compared to the saline group (95% CI: 0.62 to 1.23, p = 0.430). They were both statistically not significant. In our study, the replacement of using G-Rinse medium solution to physiologic saline solution for cervical cleaning did not change CPR and LBR outcomes. Using physiologic saline solution can be a good alternative approach for ectocervical washing during embryo transfer in selected population because of its lower costs, easy accessibility, and common use.

Pregnancy outcomes with donor oocyte embryos in patients diagnosed with adenomyosis using the Morphological Uterus Sonographic Assessment criteria

To use the Morphological Uterus Sonographic Assessment (MUSA) criteria to evaluate the impact of adenomyosis on the live birth rate after donor egg embryo transfer. Retrospective cohort study. Tertiary fertility care center. A total of 100 patients who received 223 donor embryo transfers from January 2014-2020. All patients underwent ultrasound before their first transfer. None. Our study was powered (80%) to assess the primary outcome of live birth rate; the secondary outcomes included the clinical pregnancy, biochemical pregnancy, and miscarriage rates. Only 22 of 100 patients were diagnosed with adenomyosis on the original ultrasound report. When the MUSA criteria were applied, 76 patients had at least 1 possible ultrasonographic feature of adenomyosis; all 76 patients had an interrupted junctional zone. The second most common feature of adenomyosis was a globular and/or enlarged uterus (89.4%). Adjusted modeling demonstrated that a single ultrasound feature, 2 or more features, specific features, or the location of features did not affect the live birth outcome. A per-centimeter increase in the diameter of focal lesions was significantly associated with a decrease in the odds of live birth by the factor of 0.91. To our knowledge, our study is the first to characterize adenomyosis using the MUSA criteria in the donor oocyte population. Overall, our data were reassuring in that the ultrasonographic features of adenomyosis may not impact reproductive outcomes. However, we identified that the location and size of focal lesions may be important and should be studied further.

P-683 High Serum Progesterone Levels on Day of Embryo Transfer for Pregnancy Outcomes in Patients Undergoing Artificial Frozen-thawed Blastocyst Transfer; Is There a Ceiling Effect?

Abstract Study question Is there a ceiling effect of high serum progesterone levels on day of embryo transfer for pregnancy outcomes in patients undergoing artificial frozen-thawed blastocyst transfer? Summary answer There is no ceiling effect of high serum progesterone levels on day of embryo transfer(&amp;gt;40 ng/mL)for pregnancy outcomes in patients undergoing artificial frozen-thawed blastocyst transfer. What is known already In recent studies, 10 ng/mL was usually used as the lower threshold value for serum progesterone (P4) level on the day of embryo transfer in patients undergoing artificial frozen-thawed blastocyst transfers and pregnancy outcomes were compared between patients with P4 levels above and below this threshold. The main reason for choosing this threshold in the studies is that it reflects the healthy corpus luteum function. Although many studies have investigated the lower threshold value, there is paucity of data on the high threshold value that can indicate the possible ceiling effect of P4 in the literature. Study design, size, duration This was a retrospective cohort study including 595 patients undergoing artificial frozen-thawed blastocyst transfer between 2017 to 2021. In order to eliminate the age-related bias, only patients performed euploid embryo transfer according to preimplantation genetic testing for aneuploidy from patients above aged 35 years were included. Participants/materials, setting, methods When we evaluated the percentiles of according to the progesterone levels,40.6 ng/ml corresponded to 90th percentile and 23.9 ng/ml corresponded to 50th percentile. Based on this finding, rounding up the numbers, we determined the progesterone levels cut-off as &amp;lt; 20ng/mL,n=220(37.0%);20-40ng/mL,n=312(52.4%) and ≥40ng/mL,n=63(10.6%). The main outcome measure was pregnancy outcomes as clinical pregnancy and live birth rate. We compared pregnancy outcomes according to age, BMI, blastocyst expansion, trophectoderm and inner cell mass grade and progesterone cut-off levels . Main results and the role of chance The median age of the patients was 31 (Range 20-46) and the mean body mass index (BMI) of the patients was 24.5±4.0 kg/m2. The overall clinical pregnancy rate and live birth rate were 61.8% (368/595) and 52.9% (315/595), respectively. Patients were subdivided into two different groups according to clinical pregnancy and live birth rate outcomes as follows; positive and negative. Age and BMI of patients were comparable between groups. Blastocyst morphology grade as expansion, trophectoderm and inner cell mass grade are statistically significantly associated with clinical pregnancy (p&amp;lt;.001 for all) and progesterone level between 20-40ng/mL is associated with higher clinical pregnancy rate (p:0.043). In multivariate analysis; only blastocyst expansion and inner cell mass grade were the independently and significantly factors that are associated with clinical pregnancy rate (p:0.011, OR: 1.6, CI95%: 1.13-2.39 and p:0.007, OR: 1.65, CI95%: 1.14-2.39, respectively). Progesterone level and trophectoderm grade were not fount statistically significant (p: 0.310 and p:0.489, respectively). In evaluation of the association between factors and live birth rate, only blastocyst expansion grade equal or over 4 and trophectoderm grade A or B were associated with statistically significant live birth rates. Limitations, reasons for caution The main limitations of current study were the retrospective design and the limited sample size of the ≥40 ng/mL cohort of serum progesterone levels. Wider implications of the findings According to this data, we speculated that if the serum P4 level is above 40 ng/mL on the day of embryo transfer in patients undergoing artificial frozen-thawed blastocyst transfer, there is no need to reduce the dose of progesterone used. Trial registration number N/A

Pentoxifylline for the treatment of endometriosis-associated pain and infertility.

Endometriosis is a chronic inflammatorycondition that occurs during the reproductive years. It is characterised by endometrium-liketissue developing outside the uterine cavity. This endometriotictissue development is dependent on oestrogen produced primarily by the ovaries and partially by the endometriotic tissue itself, therefore traditional management has focused on ovarian suppression. In this review we considered the role of modulation of the immune system as an alternative approach. This is an update of a Cochrane Review previously published in 2012. To determine the effectiveness and safety of pentoxifylline in the management of endometriosis. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility (CGF) Group Trials Register, CENTRAL, MEDLINE, Embase, PsycINFO, and AMED on 16 December 2020,together with reference checking and contact with study authors and experts in the field to identify additional studies. We included randomised controlled trials (RCTs) comparing pentoxifylline with placebo or no treatment, other medical treatment, or surgery in women with endometriosis. The primary outcomes were live birth rate and overall pain (as measured by a visual analogue scale (VAS) of pain, other validated scales, or dichotomous outcomes) per woman randomised. Secondary outcomes included clinical pregnancy rate, miscarriage rate, rate of recurrence, and adverse events resulting from the pentoxifylline intervention. Two review authors independently assessed studies against the inclusion criteria, extracted data, and assessed risk of bias, consulting a third review author where required. We contacted study authors as needed. We analysed dichotomous outcomes using Mantel-Haenszel risk ratios (RRs), 95% confidence intervals (CIs), and a fixed-effect model. For small numbers of events, we used a Peto odds ratio (OR) with 95% CI instead. We analysed continuous outcomes using the mean difference (MD) between groups presented with 95% CIs. We used the I2 statistic to evaluate heterogeneity amongst studies. We employed the GRADE approach to assess the quality of the evidence. We included five parallel-design RCTs involving a total of 415 women. We included one additional RCT in this update. Three studies did not specify details relating to allocation concealment, and two studies were not blinded. There were also considerable loss to follow-up, with four studies not conducting intention-to-treat analysis. We judged the quality of the evidence as very low. Pentoxifylline versus placebo No trials reported on our primary outcomes of live birth rate and overall pain. We are uncertain as to whether pentoxifylline treatment affects clinical pregnancy rate when compared to placebo (RR 1.38, 95% CI 0.91 to 2.10; 3 RCTs, n = 285; I2 = 0%; very low-quality evidence). The evidence suggests that if the clinical pregnancy rate with placebo is estimated to be 20%, then the rate with pentoxifylline is estimated as between 18% and 43%. We are also uncertain as to whether pentoxifylline affects the recurrence rate of endometriosis (RR 0.84, 95% CI 0.30to 2.36; 1 RCT, n = 121;very low-quality evidence) or miscarriage rate (Peto OR1.99, 95% CI 0.20 to 19.37; 2 RCTs, n = 164; I2 = 0%; very low-quality evidence). No trials reported on the effect of pentoxifylline on improvement of endometriosis-related symptoms other than pain or adverse events. Pentoxifylline versus no treatment No trials reported on live birth rate. We are uncertain as to whether pentoxifylline treatment affects overall pain when compared to no treatment at one month (MD -0.36, 95% CI -2.12 to 1.40; 1 RCT, n = 34; very low-quality evidence), two months (MD -1.25, 95% CI -2.67 to 0.17; 1 RCT, n = 34; very low-quality evidence), or three months (MD -1.60, 95% CI -3.32 to 0.12; 1 RCT, n = 34; very low-quality evidence). No trials reported on adverse events caused by pentoxifylline or any of our other secondary outcomes. Pentoxifylline versus other medical therapies One study (n = 83) compared pentoxifylline to the combined oral contraceptive pill after laparoscopic surgery to treat endometriosis, but could not be included in the meta-analysisas it was unclear if the data were presented as +/- standard deviation and what the duration of treatment was. No trials reported on adverse events caused by pentoxifylline or any of our other secondary outcomes. Pentoxifylline versus conservative surgical treatment No study reported on this comparison. No studies reported on our primary outcome of live birth rate. Due to the very limited evidence, we are uncertain of the effects of pentoxifylline on clinical pregnancy rate, miscarriage rate, or overall pain. There is currently insufficient evidence to support the use of pentoxifylline in the management of women with endometriosis with respect to subfertility and pain relief outcomes.

Effect of LHCGR Gene Polymorphism (rs2293275) on LH Supplementation Protocol Outcomes in Second IVF Cycles: A Retrospective Study

Infertility is a major concern for couples wanting to have progeny. Despite recent advances in the field of IVF, success rates still need improvement. Understanding the patient’s variability and addressing it with personalized interventions may improve the success rate of fertilization and live births. This study examined the impact of a personalized pharmacogenomic approach on LH supplementation on the pregnancy and live birth rate outcomes in comparison with the traditional approaches. 193 patients undergoing a second IVF cycle in Krishna IVF Clinic received LH supplementation either as per the conventional methods or based on N312S (rs2293275) LHCGR gene polymorphism. Results showed a significant increase in pregnancy rate (P-value: 0.049) and a trend showing improvement in live birth rates (P-value: 0.082) when r-hLH supplementation protocol was decided as per the genotypes A/A, A/G, and G/G of the N312S variant in the respective patients. This stimulation regimen helped in providing optimum levels of r-hLH supplementation to patients with impaired hormone-receptor interacting activity, to achieve higher success in pregnancy and live birth rates.

Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI).

Monitoring of in vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) is necessary to detect as well as reducethe incidence and severity of ovarian hyperstimulation syndrome (OHSS) whilst achieving the optimal ovarian response needed for assisted reproduction treatment. Traditional monitoring of ovarian hyperstimulation during in vitro fertilisation IVFand ICSItreatment has included transvaginal ultrasonography (TVUS) plus serum estradiol levels. The need for combined monitoring (using TVUS and serum estradiol) during ovarian stimulation in assisted reproduction is controversial. It has been suggested that combined monitoring is time consuming, expensive and inconvenient for women and that simplification of IVF and ICSI therapy by using TVUS only should be considered. OBJECTIVES: To assess the effect of monitoring controlled ovarian hyperstimulation (COH) in IVF and ICSI cycles in subfertile couples with TVUS only versus TVUS plus serum estradiol concentration, with respect to rates of live birth, pregnancy and OHSS. In this update conducted in March 2020, two review authorssearched the Cochrane Gynaecology and Fertility Group's Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, the National Research Register, and web-based trial registers. There was no language restriction applied. All references in the identified trials and background papers were checked and authors were contacted to identify relevant published and unpublished data. Only randomised controlled trials that compared monitoring with TVUS only versus TVUS plus serum estradiol concentrations in women undergoing COH for IVF and ICSI treatment were included. Two review authors (IK, AW) independently selected the studies, extracted data and assessed risk of bias. We resolved disagreements by discussion. Outcomes data were pooled and summary statistics were presented when appropriate. The quality of the evidence was rated using the GRADE methods. We did not identify any new eligible studies in this update in 2020. The evidence based on the six trials identified in 2014 remained unchanged. They included 781 women undergoing monitoring of COH with either TVUS alone or a combination of TVUS and serum estradiol concentration during IVF or ICSI treatment. None of the six studies reported our primary outcome of live birth rate. Two studies presented pregnancy rate per initiated cycle and per embryo transfer, respectively. Four studies reported pregnancy rate per woman with pooled data; we are uncertain of the effect ofmonitoring with TVUS only versus combined monitoring on clinical pregnancy rate per woman(odds ratio (OR) 1.10; 95% confidence interval (CI) 0.79 to 1.54; four studies; N = 617; I² = 5%; low quality evidence). This suggests in women with a 36% chance of clinical pregnancy using monitoring with TVUS plus serum estradiol, the clinical pregnancy rate using TVUS only would be between 31% and 46%. We are uncertain of any effectin the mean number of oocytes retrieved per woman (mean difference (MD) 0.32; 95% CI -0.60 to 1.24; five studies; N = 596; I² = 17%; low quality evidence). We are uncertain whethermonitoring with TVUS only versus combined monitoring affectedthe incidence of OHSS (OR 1.03; 95% CI 0.48 to 2.20; six studies; N = 781; I² = 0%; low quality evidence), suggesting that in women with a 4% chance of OHSS using monitoring with TVUS plus serum estradiol, the OHSS rate monitored by TVUS only would be between 2% and 8%. The cycle cancellation rate was similar in both arms of two studies (0/34 versus 1/31, 1/25 versus 1/25; OR 0.57; 95% CI 0.07 to 4.39; N = 115; I² = 0%; low quality evidence). The evidence was low quality for all comparisons. Limitations included imprecision and potential bias due to unclear randomisation methods, allocation concealment and blinding, as well as differences in treatment protocols. Quality assessment was hampered by the lack of methodological descriptions in several studies. This review update found no new randomised trials. Evidence from the six studies previously identified did not suggest that combined monitoring by TVUS and serum estradiol is more efficacious than monitoring by TVUS alone with regard to clinical pregnancy rates and the incidence of OHSS. The number of oocytes retrieved appeared similar for both monitoring protocols. The data suggest that both these monitoring methods are safe and reliable. However, these results should be interpreted with caution because the overall quality of the evidence was low. Results were compromised by imprecision and poor reporting of study methodology.The choice of one or the other method may depend upon the convenience of its use, and the associated costs.An economic evaluation of the costs involved with the two methods and the views of the women undergoing cycle monitoring would be welcome.

Effect of antithyroid antibodies on women with recurrent miscarriage: A meta-analysis.

ProblemThe effect of thyroid autoimmunity (TAI) on the prevalence of recurrent miscarriage (RM) is highly debatable. No meta‐analysis has been published in the past decade to investigate the impact of TAI on women with RM.Method of StudySystemic literature search was conducted on PubMed, Embase, Cochrane, and Web of Science databases. English language literatures published between 1993 and 2019 were selected. We assessed the relationship between the prevalence of RM and thyroid peroxidase antibodies (TPO‐Ab) or antithyroid antibodies (ATA) and evaluated the thyroid‐stimulating hormone (TSH) level in TPO‐Ab‐positive women with RM. We also observed the treatment effect with levothyroxine (LT4) for RM. Review Manager 5.3 software was used to obtain the pooled odds ratios (OR).ResultsAnalysis of 22 eligible studies revealed significant association between TPO‐Ab and the prevalence of RM (OR = 1.85; 95% CI, 1.38 to 2.49; P < .001)(n ≥ 3), (OR = 1.82; 95% CI, 1.13 to 2.92; P = .01) (n ≥ 3). Women with ATA + had higher risk of RM (OR = 2.36; 95% CI, 1.71 to 3.25; P < .00001)(n ≥ 3), (OR = 2.34; 95% CI, 1.70 to 3.22; P < .00001)(n ≥ 2). RM women with TPO‐Ab had higher TSH level when compared with those negative for TPO‐Ab (random‐effect SMD = 0.60; 95% CI, 0.31 to 0.90; P < .0001). We also found beneficial effects of LT4 supplementation on the outcome of live birth rate (LBR) among pregnant women with TPO‐Ab (OR = 3.04; 95% CI, 0.69 to 13.36; P = .14).ConclusionThe presence of serum antithyroid antibodies does harms to women and can even lead to recurrent miscarriage; LT4 treatment may have beneficial to RM women.

Administration of Antioxidants in the Infertile Male: When it may have a Beneficial Effect?

Reactive Oxygen Species (ROS) are required for intact spermatogenesis and sperm function, but excessive levels will cause oxidative stress, impairing sperms and sperm function due to membrane damage and DNA fragmentation. Theoretically, antioxidant supplementation may act as a protection system against free radicals. Since infertile males have higher levels of ROS, nutritional supplements are widely used for protecting sperms. In the recent review, the authors summarize the most recent data regarding the effect of antioxidant treatment and draw the attention of the limitations of antioxidant use in male infertility. The recent review gives an update of antioxidant treatment in male infertility. Improvement of sperm parameters was reported in the majority of studies. Comparing different antioxidants versus placebo showed low certainty of evidence with a serious risk of bias, and there is a lack regarding certain doses, pregnancy rate, and live birth rate outcomes. Various clinical studies and randomized control trials reported negative outcomes. Conflicting findings lead the attention to the study of biochemical features of the oxidant vs. antioxidant equilibrium. Higher exposure to antioxidants will result in "reductive stress", which has harmful effects on sperm function, moreover can negatively influence embryo development. Reductive stress is as dangerous as oxidative stress and may act as a cause of different human pathologies. An intact balance of oxidant and antioxidant systems is required for normal sperm function. No guideline exists for the antioxidant dose regimen and treatment duration. Overdosing can result in reductive stress, which is also harmful to fertility and can cause several diseases. Assessment of the pre-treatment redox status can be recommended before the administration of exogenous antioxidants.

Efficacy, safety and tolerability of progesterone vaginal pessaries versus progesterone vaginal gel for luteal phase support after in vitro fertilisation: a randomised controlled trial.

Efficacy, safety and tolerability of progesterone vaginal pessaries versus progesterone vaginal gel for luteal phase support after in vitro fertilisation: a randomised controlled trial.

Progestogen for preventing miscarriage in women with recurrent miscarriage of unclear etiology.

Progesterone, a female sex hormone, is known to induce secretory changes in the lining of the uterus essential for successful implantation of a fertilized egg. It has been suggested that a causative factor in many cases of miscarriage may be inadequate secretion of progesterone. Therefore, clinicians use progestogens (drugs that interact with the progesterone receptors), beginning in the first trimester of pregnancy, in an attempt to prevent spontaneous miscarriage. This is an update of a review, last published in 2013. Since publication of the 2018 update of this review, we have been advised that the Ismail 2017 study is currently the subject of an investigation by the Journal of Maternal-Fetal & Neonatal Medicine. We have now moved this study from 'included studies' to 'Characteristics of studies awaiting classification' until the outcome of the investigation is known. To assess the efficacy and safety of progestogens as a preventative therapy against recurrent miscarriage. For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (6 July 2017) and reference lists from relevant articles, attempting to contact trial authors where necessary, and contacted experts in the field for unpublished works. Randomized or quasi-randomized controlled trials comparing progestogens with placebo or no treatment given in an effort to prevent miscarriage. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Two reviewers assessed the quality of the evidence using the GRADE approach. Twelve trials (1,856 women) met the inclusion criteria. Eight of the included trials compared treatment with placebo and the remaining four trials compared progestogen administration with no treatment. The trials were a mix of multicenter and single-center trials, conducted in India, Jordan, UK and USA. In five trials women had had three or more consecutive miscarriages and in seven trials women had suffered two or more consecutive miscarriages. Routes, dosage and duration of progestogen treatment varied across the trials. The majority of trials were at low risk of bias for most domains. Ten trials (1684 women) contributed data to the analyses. The meta-analysis of all women, suggests that there may be a reduction in the number of miscarriages for women given progestogen supplementation compared to placebo/controls (average risk ratio (RR) 0.73, 95% confidence interval (CI) 0.54 to 1.00, 10 trials, 1684 women, moderate-quality evidence). A subgroup analysis comparing placebo-controlled versus non-placebo-controlled trials, trials of women with three or more prior miscarriages compared to women with two or more miscarriages and different routes of administration showed no clear differences between subgroups for miscarriage. None of the trials reported on any secondary maternal outcomes, including severity of morning sickness, thromboembolic events, depression, admission to a special care unit, or subsequent fertility. There was probably a slight benefit for women receiving progestogen seen in the outcome of live birth rate (RR 1.07, 95% CI 1.00 to 1.13, 6 trials, 1411 women, moderate-quality evidence). We are uncertain about the effect on the rate of preterm birth because the evidence is very low-quality (RR 1.13, 95% CI 0.53 to 2.41, 4 trials, 256 women, very low-quality evidence). No clear differences were seen for women receiving progestogen for the other secondary outcomes including neonatal death, fetal genital abnormalities or stillbirth. There may be little or no difference in the rate of low birthweight and trials did not report on the secondary child outcomes of teratogenic effects or admission to a special care unit. For women with unexplained recurrent miscarriages, supplementation with progestogen therapy may reduce the rate of miscarriage in subsequent pregnancies.

Progestogen for preventing miscarriage in women with recurrent miscarriage of unclear etiology.

Progesterone, a female sex hormone, is known to induce secretory changes in the lining of the uterus essential for successful implantation of a fertilized egg. It has been suggested that a causative factor in many cases of miscarriage may be inadequate secretion of progesterone. Therefore, clinicians use progestogens (drugs that interact with the progesterone receptors), beginning in the first trimester of pregnancy, in an attempt to prevent spontaneous miscarriage. This is an update of a review, last published in 2013. To assess the efficacy and safety of progestogens as a preventative therapy against recurrent miscarriage. For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (6 July 2017) and reference lists from relevant articles, attempting to contact trial authors where necessary, and contacted experts in the field for unpublished works. Randomized or quasi-randomized controlled trials comparing progestogens with placebo or no treatment given in an effort to prevent miscarriage. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Two reviewers assessed the quality of the evidence using the GRADE approach. Thirteen trials (2556 women) met the inclusion criteria. Nine of the included trials compared treatment with placebo and the remaining four trials compared progestogen administration with no treatment. The trials were a mix of multicenter and single-center trials, conducted in Egypt, India, Jordan, UK and USA. In six trials women had had three or more consecutive miscarriages and in seven trials women had suffered two or more consecutive miscarriages. Routes, dosage and duration of progestogen treatment varied across the trials. The majority of trials were at low risk of bias for most domains. Eleven trials (2359 women) contributed data to the analyses.The meta-analysis of all women, suggests that there is probably a reduction in the number of miscarriages for women given progestogen supplementation compared to placebo/controls (average risk ratio (RR) 0.69, 95% confidence interval (CI) 0.51 to 0.92, 11 trials, 2359 women, moderate-quality evidence). A subgroup analysis comparing placebo-controlled versus non-placebo-controlled trials and different routes of administration showed no differences between subgroups for miscarriage. However, there appears to be a subgroup difference for miscarriage between women with three or more prior miscarriages compared to women with two or more miscarriages, with a more pronounced effect in women with three or more prior miscarriages. However, it should be noted that there was high heterogeneity in the subgroup of women with three or more prior miscarriages.None of the trials reported on any secondary maternal outcomes, including severity of morning sickness, thromboembolic events, depression, admission to a special care unit, or subsequent fertility.There was probably a slight benefit for women receiving progestogen seen in the outcome of live birth rate (RR 1.11, 95% CI 1.00 to 1.24, 7 trials, 2086 women, moderate-quality evidence). While the rate of preterm birth is probably reduced for women receiving progestogen, this outcome was mainly driven by one trial and thus should be interpreted with great caution (RR 0.59, 95% CI 0.39 to 0.89, 5 trials, 811 women, moderate-quality evidence). No clear differences were seen for women receiving progestogen for the other secondary outcomes of neonatal death or fetal genital abnormalities. A possible reduction in stillbirth was seen, but again this outcome was driven mainly by one trial and should be interpreted with caution (RR 0.38, 95% CI 0.24 to 0.58, 3 trials, 1199 women). There may be little or no difference in the rate of low birthweight and trials did not report on the secondary child outcomes of teratogenic effects or admission to a special care unit. For women with unexplained recurrent miscarriages, supplementation with progestogen therapy probably reduces the rate of miscarriage in subsequent pregnancies.

Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI).

Traditional monitoring of ovarian hyperstimulation during in vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) treatment has included transvaginal ultrasonography (TVUS) plus serum estradiol levels to ensure safe practice by reducing the incidence and severity of ovarian hyperstimulation syndrome (OHSS) whilst achieving the good ovarian response needed for assisted reproduction treatment. The need for combined monitoring (using TVUS and serum estradiol) during ovarian stimulation in assisted reproduction is controversial. It has been suggested that combined monitoring is time consuming, expensive and inconvenient for women and that simplification of IVF and ICSI therapy by using TVUS only should be considered. To assess the effect of monitoring controlled ovarian hyperstimulation (COH) in IVF and ICSI cycles in subfertile couples with TVUS only versus TVUS plus serum estradiol concentration, with respect to rates of live birth, pregnancy and OHSS. We searched the Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, the National Research Register, and web-based trial registers such as Current Controlled Trials. The last search was conducted in May 2014. There was no language restriction applied. All references in the identified trials and background papers were checked and authors were contacted to identify relevant published and unpublished data. Only randomised controlled trials that compared monitoring with TVUS only versus TVUS plus serum estradiol concentrations in women undergoing COH for IVF and ICSI treatment were included. Three review authors independently selected the studies, extracted data and assessed risk of bias. They resolved disagreements by discussion with the rest of the authors. Outcomes data were pooled and summary statistics were presented when appropriate. The quality of the evidence was rated using the GRADE methods. With this update, four new studies were identified resulting in a total of six trials including 781 women undergoing monitoring of COH with either TVUS alone or a combination of TVUS and serum estradiol concentration during IVF or ICSI treatment.None of the six studies reported our primary outcome of live birth rate. Pooled data showed no evidence of a difference in clinical pregnancy rate per woman between monitoring with TVUS only and combined monitoring (odds ratio (OR) 1.10; 95% confidence interval (CI) 0.79 to 1.54; four studies; N = 617; I² = 5%; low quality evidence). This suggests that compared with women with a 34% chance of clinical pregnancy using monitoring with TVUS plus serum estradiol, the clinical pregnancy rate in women using TVUS only was between 29% and 44%.There was no evidence of a difference between the groups in the reported cases of OHSS (OR 1.03; 95% CI 0.48 to 2.20; six studies; N = 781; I² = 0%; low quality evidence), suggesting that compared with women with a 4% chance of OHSS using monitoring with TVUS plus serum estradiol, the OHSS rate in women monitored by TVUSS only was between 2% and 8%.There was no evidence of a difference between the groups in the mean number of oocytes retrieved pre woman (mean difference (MD) 0.32; 95% CI -0.60 to 1.24; five studies; N = 596; I² = 17%; low quality evidence).The evidence was low quality for all comparisons. Limitations included imprecision and potential bias due to unclear randomisation methods, allocation concealment and blinding, as well as differences in treatment protocols. Quality assessment was hampered by the lack of methodological descriptions in several studies. This review update found no evidence from randomised trials to suggest that combined monitoring by TVUS and serum estradiol is more efficacious than monitoring by TVUS alone with regard to clinical pregnancy rates and the incidence of OHSS. The number of oocytes retrieved appeared similar for both monitoring protocols. The data suggest that both these monitoring methods are safe and reliable. However, these results should be interpreted with caution because the overall quality of the evidence was low. Results were compromised by imprecision and poor reporting of study methodology. A combined monitoring protocol including both TVUS and serum estradiol may need to be retained as precautionary good clinical practice and as a confirmatory test in a subset of women to identify those at high risk of OHSS. An economic evaluation of the costs involved with the two methods and the views of the women undergoing cycle monitoring would be welcome.

Laparoscopic drilling by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome

Surgical ovarian wedge resection was the first established treatment for women with anovulatory polycystic ovary syndrome (PCOS) but was largely abandoned both due to the risk of postsurgical adhesions and the introduction of medical ovulation induction. However, women with PCOS who are treated with medical ovulation induction, with drugs such as gonadotrophins, often have an over-production of follicles which may result in ovarian hyperstimulation syndrome and multiple pregnancies. Moreover, gonadotrophins, though effective, are costly and time-consuming and their use requires intensive monitoring. Surgical therapy with laparoscopic ovarian 'drilling' (LOD) may avoid or reduce the need for medical ovulation induction, or may facilitate its usefulness. The procedure can be done on an outpatient basis with less trauma and fewer postoperative adhesions than with traditional surgical approaches. Many uncontrolled observational studies have claimed that ovarian drilling is followed, at least temporarily, by a high rate of spontaneous ovulation and conception, or that subsequent medical ovulation induction becomes easier. To determine the effectiveness and safety of laparoscopic ovarian drilling compared with ovulation induction for subfertile women with clomiphene-resistant PCOS. We used the search strategy of the Menstrual Disorders and Subfertility Group (MDSG) to search the MDSG Trials Register, CENTRAL, MEDLINE, EMBASE, CINAHL and PsycINFO. The keywords included polycystic ovary syndrome, laparoscopic ovarian drilling, electrocautery and diathermy. Searches were conducted in September 2011, and a further search of the MDSG Trials Register was made on 14 May 2012. We included randomised controlled trials of subfertile women with clomiphene-resistant PCOS who undertook laparoscopic ovarian drilling in order to induce ovulation. This is an update of a previously updated review. There were nine RCTs in the previous version; an additional 16 trials were added in the current (2012) update. All trials were assessed for quality. The primary outcomes were live birth and multiple pregnancy. The secondary outcomes were rate of miscarriage, ovulation and pregnancy rates, ovarian hyperstimulation syndrome (OHSS), quality of life and cost. Nine trials, including 1210 women, reported on the primary outcome of live birth rate per couple. Live births were reported in 34% of women in the LOD groups and 38% in other medical treatment groups. There were five different comparisons with LOD and there was no evidence of a difference in live births when compared with clomiphene citrate + tamoxifen (OR 0.81; 95% CI 0.42 to 1.53; P = 0.51, 1 trial, n = 150), gonadotrophins (OR 0.97; 95% CI 0.59 to 1.59; P = 0.89, I(2) = 0%, 2 trials, n = 318), aromatase inhibitors (OR 0.84; 95% CI 0.54 to 1.31; P = 0.44, I(2) = 0%, 2 trials, n = 407) or clomiphene citrate (OR 1.21; 95%CI 0.64 to 2.32; 1 trial, n=176, P= 0.05). There was evidence of significantly fewer live births following LOD compared with clomiphene citrate + metformin (OR 0.44; 95% CI 0.24 to 0.82; P = 0.01, I(2) = 78%, 2 trials, n = 159); the high heterogeneity in this subgroup could not be explained by population differences or differences in quality of the trials.Thirteen trials reported on multiple pregnancies (n= 1305 women). There were no cases of multiple pregnancies in either group for clomiphene citrate or aromatase inhibitors compared with LOD. The rate of multiple pregnancies was significantly lower in the LOD group compared with trials using gonadotrophins (OR 0.13; 95% CI 0.03 to 0.52; P=0.004, I(2) = 0%, 5 trials, n = 166). There was no evidence of a significant difference in rates of clinical pregnancy, live birth or miscarriage in women with clomiphene-resistant PCOS undergoing LOD compared to other medical treatments. The reduction in multiple pregnancy rates in women undergoing LOD makes this option attractive. However, there are ongoing concerns about the long-term effects of LOD on ovarian function.

Urinary hMG versus recombinant FSH for controlled ovarian hyperstimulation following an agonist long down-regulation protocol in IVF or ICSI treatment: a systematic review and meta-analysis

Since the most recent Cochrane review on hMG versus rFSH for controlled ovarian hyperstimulation following a long down-regulation protocol, several new trials have emerged. We conducted a systematic review and meta-analysis of randomized trials comparing the effectiveness of hMG versus rFSH following a long down-regulation protocol in IVF-ICSI cycles, on the primary outcome of live birth per woman randomized, as well as several other secondary outcomes. Searches were conducted in MEDLINE, EMBASE, Science Direct, Cochrane Library and databases of abstracts (last search January 2007). Seven randomized trials, consisting of a total of 2159 randomized women, were identified. A meta-analysis of these trials showed a significant increase in live birth rate with hMG when compared with rFSH (relative risk, RR = 1.18, 95% CI: 1.02-1.38, P = 0.03). The heterogeneity test was non-significant (P = 0.97), suggesting that there was no statistical inconsistency between the seven studies. The pooled risk difference (RD) for the outcome of live birth rate was 4% (95% CI: 1-7%) for these study populations. There was an increase in clinical pregnancy rates with hMG when compared with rFSH (RR = 1.17, 95% CI 1.03-1.34). No significant differences were noted for gonadotrophin use, spontaneous abortion, multiple pregnancy, cancellation and ovarian hyperstimulation syndrome rates. For the populations in the randomized trials, hMG was associated with a pooled 4% increase in live birth rate when compared with rFSH in IVF-ICSI treatment following a long down-regulation protocol.

Preimplantation genetic screening for abnormal number of chromosomes (aneuploidies) in in vitro fertilisation or intracytoplasmic sperm injection

In both in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), selection of the most competent embryo(s) for transfer is generally based on morphological criteria. However, many women fail to achieve a pregnancy after transfer of good quality embryos. One of the presumed causes is that such morphologically normal embryos show an abnormal number of chromosomes (aneuploidies). In preimplantation genetic screening (PGS), embryos are analysed for aneuploidies and only embryos that are euploid for the chromosomes tested are transferred. This technique has been suggested and used to improve pregnancy rates for the following indications: (i) advanced maternal age, (ii) repeated IVF failure, (iii) repeated miscarriage and (iv) testicular sperm extraction (TESE)-ICSI. Although PGS is used more and more often, its effectiveness is still unclear. To assess the effectiveness of PGS in terms of live births in women undergoing IVF or ICSI treatment. We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 1, 2005), MEDLINE (1966 to present) and EMBASE (1980 to present) (searched March 2005) and reference lists of articles. We also contacted authors for providing additional data when necessary. Trials for all four suggested indications as mentioned above were sought. All relevant published randomised controlled trials were selected. They were eligible for inclusion if the comparison dealt with IVF/ICSI with PGS versus IVF/ICSI without PGS. Relevant data were extracted independently by two authors. All trials were screened and analysed according to predetermined quality criteria. Validity was assessed in terms of method of randomisation, completeness of follow-up, intention-to-treat analysis and presence or absence of blinding. The primary outcome measure was live birth rate per woman. Secondary outcome measures were the proportion of women reaching embryo transfer, mean number of embryos transferred per transfer, clinical pregnancy rate, multiple pregnancy rate, miscarriage rate, ongoing pregnancy rate, proportion of women reaching embryo transfer after cryopreservation and proportion of women whose child has a congenital malformation. Two randomised controlled trials met our predetermined eligibility criteria. These trials used PGS for advanced maternal age. The primary outcome of live birth rate per woman was not significantly different in the PGS and control groups, though data were only available from one study. The live birth rate was 11% (21 out of 199) in the PGS group, versus 15% (29 out of 190) in the control group (OR 0.65; 95% CI 0.36 to 1.19). For a control group rate of 15%, these data suggest a live birth rate using PGS of between 4% and 17%. Ongoing pregnancy rate was provided in both studies. This was not significantly different with a combined odds ratio of 0.64 (95% CI 0.37 to 1.09). For a control group rate of 20%, this suggests an ongoing pregnancy rate using PGS of between 8% and 21%. To date there is insufficient data to determine whether PGS is an effective intervention in IVF/ICSI for improving live birth rates. Available data on PGS for advanced maternal age showed no difference in live birth rate and ongoing pregnancy rate. However, only two randomised trials were found, of which one included only 39 patients. For both studies comments on their methodological quality can be made. Therefore more properly conducted randomised controlled trials are needed. Until such trials have been performed PGS should not be used in routine patient care.