Clinical guidelines for prevention and management of preterm birth: a systematic review.

BACKGROUND: Clinical practice guidelines (CPG) endorse multiple strategies to prevent or manage preterm birth (PTB). OBJECTIVES: To summarise CPG recommendations for PTB and identify areas of international consensus. SEARCH STRATEGY: In May 2017 we searched for all CPG relevant to PTB without language restrictions. SELECTION CRITERIA: CPG were eligible if the following criteria were met: (1) the guideline was published or current from June 2013; (2) the guideline recommended practices for the prevention or management of PTB relevant to our prespecified clinical questions for screening, medications or surgery and other interventions; (3) publications on methods of guideline development for eligible CPG were included to enable quality assessment. DATA COLLECTION AND ANALYSIS: Two authors classified CPG recommendations relevant to prespecified clinical questions. When more than 70% of CPGs reporting on a topic recommended or rejected an intervention, we regarded this as consensus. We summarised recommendations in tables. MAIN RESULTS: We identified 49 guidelines from 16 guideline developers. We found consensus for several clinical practices: cervical length screening for high-risk women; short-term tocolysis; steroids for fetal lung maturation; and magnesium sulphate for fetal neuroprotection. We found discrepant recommendations for progesterone and fibronectin. No guideline identified an effective strategy for women with multiple pregnancy. CONCLUSIONS: We identified interventions for which there is an international consensus on benefit for PTB. Systematic reviews of CPG using standardised methodology will help avoid duplication and target scarce resources for guideline developers globally. TWEETABLE ABSTRACT: International clinical guidelines agree on the benefits and harmful effects of several important interventions to prevent preterm birth.

Methods to induce labour: a systematic review, network meta-analysis and cost-effectiveness analysis.

OBJECTIVES: To compare the clinical effectiveness and cost-effectiveness of labour induction methods. METHODS: We conducted a systematic review of randomised trials comparing interventions for third-trimester labour induction (search date: March 2014). Network meta-analysis was possible for six of nine prespecified key outcomes: vaginal delivery within 24 hours (VD24), caesarean section, uterine hyperstimulation, neonatal intensive care unit (NICU) admissions, instrumental delivery and infant Apgar scores. We developed a decision-tree model from a UK NHS perspective and calculated incremental cost-effectiveness ratios, expected costs, utilities and net benefit, and cost-effectiveness acceptability curves. MAIN RESULTS: In all, 611 studies comparing 31 active interventions were included. Intravenous oxytocin with amniotomy and vaginal misoprostol (≥50 µg) were most likely to achieve VD24. Titrated low-dose oral misoprostol achieved the lowest odds of caesarean section, but there was considerable uncertainty in ranking estimates. Vaginal (≥50 µg) and buccal/sublingual misoprostol were most likely to increase uterine hyperstimulation with high uncertainty in ranking estimates. Compared with placebo, extra-amniotic prostaglandin E2 reduced NICU admissions. There were insufficient data to conduct analyses for maternal and neonatal mortality and serious morbidity or maternal satisfaction. Conclusions were robust after exclusion of studies at high risk of bias. Due to poor reporting of VD24, the cost-effectiveness analysis compared a subset of 20 interventions. There was considerable uncertainty in estimates, but buccal/sublingual and titrated (low-dose) misoprostol showed the highest probability of being most cost-effective. CONCLUSIONS: Future trials should be designed and powered to detect a method that is more cost-effective than low-dose titrated oral misoprostol. TWEETABLE ABSTRACT: New study ranks methods to induce labour in pregnant women on effectiveness and cost.

The relationship between critical evaluation of sperm morphology and the TYB-optimized zona free hamster oocyte sperm penetration assay.

The objective of this study was to analyse the relationship between the percentage of spermatozoa in semen with normal morphology, assessed using the Tygerberg criteria, and sperm fertilizing ability assessed using the TYB-optimized zona free hamster oocyte sperm penetration assay (TYB-optimized SPA), to evaluate the predictive value of strict morphology on outcome of the SPA. In a retrospective study, 56 samples were analysed. In addition to routine semen parameters, the percentage of spermatozoa with normal morphology (A forms) and the average number of penetrations per oocyte (Sperm Capacitation Index) was evaluated in all cases. Using a multiple linear regression analysis with all semen parameters, sperm morphology was the best predictor (p = 0.001) of the SPA score. The agreement between the percentage of A forms and the Sperm Capacitation Index beyond chance (kappa coefficient) was 0.5842. Twenty-two specimens had abnormal SPA scores, with 21 exhibiting abnormal sperm morphology (Sensitivity = 96%). The remaining 34 samples had normal Sperm Capacitation Index values; of these, 23 had normal sperm morphology in semen (Specificity = 68%). The positive predictive value was 96%, and the negative predictive value was 66%. All semen samples from control donors had normal semen parameters and Sperm Capacitation Index values. In conclusion, the percentage of spermatozoa with normal morphology assessed using Tygerberg criteria (> 14% A forms) are predictive of the results in the TYB-optimized SPA. However, sperm morphology appears to be a better predictor when it is normal than when it is abnormal.

Response of routine semen analysis and critical assessment of sperm morphology by Kruger classification to therapeutic varicocelectomy.

PURPOSE: We studied the effect of varicocelectomy on Kruger morphology and semen parameters. MATERIALS AND METHODS: A total of 33 subfertile men diagnosed with varicoceles was evaluated 3 months before, and 3 to 4 and 6 to 8 months after varicocelectomy. Evaluation involved routine semen analysis and sperm morphology using Kruger classification. RESULTS: Significant improvement in sperm concentration and count was found after varicocelectomy (sperm count preoperatively 117.1 +/- 29, 3 to 4 months postoperatively 162.5 +/- 41 and 6 to 8 months postoperatively 139.8 +/- 25 million sperm, p = 0.0095). Using Kruger classification, evaluation of sperm morphology revealed overall significant increase in percentage of normal A forms at 3 to 4 and 6 to 8 months after surgery (from 9.8 +/- 5.8% A forms, 13.6 +/- 7.7% A forms, and 14.5 +/- 7.5% A forms, respectively, p = 0.0002, normal greater than 14%). Twelve of the 26 patients (46%) with abnormal sperm morphology preoperatively and greater than 4% A forms reached normal levels 3 months postoperatively. Six months after surgery only 6 patients maintained normal values and 3 of the initial 14 nonresponders became normal (9 of 26, 36%). Three patients with severe teratozoospermia (less than 4% A forms) showed improvement in sperm morphology. Four patients with normal sperm morphology preoperatively were not affected by varicocelectomy. CONCLUSIONS: Surgical correction of varicocele was associated with significant improvement in sperm morphology evaluated using Kruger classification. Concentration and count improved after varicocelectomy. Changes were observed as early as 3 months after surgery.

The incidence and influence of antisperm antibodies in infertile human couples on sperm-cervical mucus interactions and subsequent fertility.

Analysis of serum samples from 698 infertile couples revealed antisperm antibodies present in 16.5% of the men and 21.6% of the women. Overall, 31.1% of the couples possessed at least one individual with positive results. Sperm-immobilized activity was detected in 29.6% of the cervical mucus (CM) samples from 459 women. Reduced sperm penetration of CM was significantly associated with serum titers of antisperm antibodies in both sexes and also with immobilizing activity in CM of women. The incidence of subsequent pregnancy in 376 infertile couples was reduced significantly if one or both partners had antisperm antibodies in serum or in genital tract secretions. The latter was reflected by evaluation of the immobilization, penetration, and shaking phenomenon of sperm in CM.

PIP: Serum antisperm antibodies were analyzed for 698 human couples with primary or secondary infertility to evaluate the incidence of antisperm antibodies in the circulation of men and women and in the cervical mucus of women as well as to evaluate the association of these antibodies with sperm penetration of cervical mucus in vitro and the relationship of these factors with subsequent fertility. Questionnaires concerning fertility status were mailed to 520 couples that had been analyzed for sperm antibodies from 1-3 years earlier. Completed questionnaires were obtained from 402 couples, and 376 of these couples were suitable for inclusion in the study. The mean duration of infertility was 4.1 +or- 2.5 years, with a range of 1-15 years for all couples; for 31 couples with secondary infertility, the duration was 3.4 +or- 1.9 years, with a range of 1.5-5.5 years. 14.8% of the men 19.6% of the women had sperm-agglutinating antibodies. An examination of the type of agglutination indicated that 88% of the positive sera showed the tail-to-tail type and the remainder showed the head-to-head type. The overall incidences of immobilizing antibody were 5.6 for men and 6.4% for women. The incidence of immobilizing antibody increased significantly in both men and women with increasing agglutination titers, as reflected by the respective correlations of 0.50 and 0.34 between the 2 tests. The incidence of pregnancy was influenced significantly by the presence of circulating sperm-agglutinating and immobilizing antibodies in both sexes. Sperm-immobilizing activity was detected in 29.6% of the cervical mucus samples from 459 women. The frequency of immobilizing antibody activity was significantly greater in samples from women with positive serum samples by either the TAT or the SIT. Sperm penetration of cervical mucus was significantly affected by the presence of either type of serum antisperm antibody in men and by sperm agglutinins in women. The incidence of subsequent pregnancy among the couples was significantly associated with each of the techniques utilized to assess antisperm antibodies. The sperm shaking phenomenon showed a significant effect that was most dramatic in those couples with more than 75% of the motile sperm exhibiting shaking in which only 1 of 13 experienced a diagnosed pregnancy. Significant but low correlation coefficients were found for the occurrence of pregnancy with the results of the serum and cervical mucus techniques. Multiple partial correlation analyses of the variables with pregnancy occurrence revealed that of the serum tests, agglutinating titers had significantly greater coefficients for men and women.

Studies on the use of estrous bovine cervical mucus in the human sperm-cervical mucus penetration technique.

Estrous bovine cervical mucus (BCM) was evaluated as a practical substitute for midcycle human cervical mucus (HCM) in the sperm-cervical mucus penetration technique (S-CMPT). Analysis of semen samples from 299 men of infertile couples suggested that up to 95% of the S-CMPT analyses with BCM were compatible with results expected with HCM. Results from a secondary S-CMPT with BCM using donor sperm treated with seminal plasma or cervical mucus extracts from partners of infertile couples indicated 70 and 88% agreement with the clinical S-CMPT obtained with the semen and cervical mucus samples, respectively. Seminal plasma samples from men with serum antisperm antibodies decreased the ability of donor sperm to penetrate BCM in the Secondary S-CMPT. Our results indicate that estrous BCM possess those basic qualities of HCM that support human sperm motility, allow for normal sperm penetration, and interact with antibody-treated sperm to inhibit penetration and to produce the sperm shaking phenomenon.