Search

Study question Is there a difference in fertility-related quality of life (QoL) in subfertile women undergoing transvaginal hydrolaparoscopy (THL) versus hysterosalpingography (HSG) as a first-line tubal-patency test? Summary answer In subfertile women undergoing first-line tubal patency testing, THL and HSG resulted in comparable fertility-related QoL. What is known already Both subfertility itself and subfertility treatment can have a significant impact on QoL. Tubal patency testing as part of fertility work-up is also known as a potential stressor. Pain scores for THL are significantly lower than for HSG (VAS 4.7 vs 5.4 ; SD: 2.5, p 0.038), but acceptability of the procedures was found to be comparable. Fertility-related QoL has not yet been studied in women undergoing tubal patency testing. Study design, size, duration We used data from a randomised clinical trial performed in 4 Dutch teaching hospitals, NTR3462. Between May 2013 and October 2016, we randomly assigned 300 subfertile women to THL or HSG with live birth as primary outcome. We performed a standardized questionnaire study as part of a randomised controlled trial comparing THL and HSG in the work-up for subfertility. Participants/materials, setting, methods Women were eligible if they were undergoing a fertility work-up with an indication for evaluation of tubal patency testing. Fertility-related QoL was measured six weeks after the procedure with the validated FertiQoL questionnaire, which produces a Core (total) score and four subscale domains: Emotional, Relational, Social, and Mind-Body. FertiQoL scores for the Core score and subscales between THL and HSG were compared using Mann-Whitney-U test and multiple linear regression analysis. Main results and the role of chance We allocated 149 women to THL and 151 to HSG. The questionnaire was completed by 84 women in the THL group (response rate 56%) and 96 women in the HSG group (response rate 64%). Core scores were 74.6 ±12.8 for THL and 73.4 ±12.4 for HSG (p = 0.39). Scores for the Emotional domain were 64.5 ±19.0 for THL versus 66.0 ±16.3 (p = 0.67) for HSG. Scores for the ‘Mind-body’ domain for THL were 76.9 ±15.6 versus 74.1 ±18.0 for HSG (p = 0.42), scores for the Relational domain were 79.2 ±12.9 for THL and 76.9 ±15.6 for HSG (p = 0.21). Scores for the Social domain for THL were 77.9 ±15.1 versus 76.7±14.1, (p = 0.42). The optional ‘Treatment FertiQol’ was completed by 156 women. Total scores were 77.5 ±12.1 for THL versus 73.8 ±13.1 (p = 0.08) for HSG. The multiple linear regression analysis showed only a statistical significant positive effect of higher age on the score for the Emotional domain (B:0.90, p = 0.015). Limitations, reasons for caution One of the main limitations of this study was a response rate of 60%. Although this is considered an acceptable rate within questionnaire research, this could lead to selection bias. Wider implications of the findings: In subfertile women, tubal patency testing with THL versus HSG did not result in differences in fertility-related QoL. Trial registration number NTR3462

One of the aims in reproductive medicine is to differentiate between couples that have favourable chances of conceiving naturally and those that do not. Since the development of the prediction model of Hunault, characteristics of the subfertile population have changed. The objective of this analysis was to assess whether additional predictors can refine the Hunault model and extend its applicability. Consecutive subfertile couples with unexplained and mild male subfertility presenting in fertility clinics were asked to participate in a prospective cohort study. We constructed a multivariable prediction model with the predictors from the Hunault model and new potential predictors. The primary outcome, natural conception leading to an ongoing pregnancy, was observed in 1053 women of the 5184 included couples 120%). All predictors of the Hunault model were selected into the revised model plus an additional seven Ivvoman's body mass index, cycle length, basal FSH levels, tubal status, history of previous pregnancies in the current relationship [ongoing pregnancies after natural conception, fertility treatment or miscarriages), semen volume, and semen morphology. Predictions from the revised model seem to concur better with observed pregnancy rates compared with the Hunault model; c-statistic of 0.71 195% CI 0.69 to 0.731 compared with 0.59 195% CI 0.57 to 0.61). (C) 2017 Published by Elsevier Ltd on behalf of Reproductive Healthcare Ltd

Objective: To assess the capacity of transvaginal hydrolaparoscopy (THL) versus hysterosalpingography (HSG) as a primary tool to diagnose tubal pathology.Study Design: We performed a multicenter RCT (NTR3462) in 4 teaching hospitals in the Netherlands, comparing THL and HSG as first line tubal test in subfertile women. The primary outcome of the trial was cumulative live birth rate at 24 months. Here, we present the secondary outcomes, the diagnostic findings of both THL and HSG as well as performance defined as failures, complications and pain- and acceptability scores.Results: Between May 2013 and October 2016, we allocated 149 women to THL and 151 to HSG, of which 17 women in the THL group (11.4%) and 12 in the HSG group (7.9%) conceived naturally before the scheduled procedure, while 13 HSGs and 5 THLs were not performed for other reasons (withdrawal of informed consent, not willing to undergo tubal testing and protocol violations). A total of 119 THLs and 134 HSGs were carried out. Failures were seen more in the THL group (n = 8, 5.6%) than in the HSG group (n = 1, 0.7%) (p = 0.014). Complications did not differ significantly between the groups (THL n =4; 2.8% vs HSG n =1; 0.7%) (p = 0.20). Bilateral tubal occlusion was detected in one versus three women (0.9% versus 2.2%) of the THL group and HSG group, while unilateral tubal occlusion was detected in seven (6.2%) versus eight (5.9%) women, respectively. Normal findings were seen in 96 (79.3%) women randomised to THL and in 119 (87.5%) in women randomised for HSG (RR 0.91 95%CI 0.81-1.01, p = 0.08). The pain score was significantly less for THL (VAS 4.7 (SD: 2.5)) than for HSG (VAS 5.4 (SD:2.5)) (p 0.038). The acceptability rate of THL and was high and comparable.Conclusion: THL and HSG have a comparable capacity in diagnosing tubal pathology with comparable performance in safety, pain and acceptability. (C) 2019 Elsevier B.V. All rights reserved.

STUDY QUESTION: Do age, ovulatory status, severity of obesity and body fat distribution affect the effectiveness of lifestyle intervention in obese infertile women? SUMMARY ANSWER: We did not identify a subgroup in which lifestyle intervention increased the healthy live birth rate however it did increase the natural conception rate in anovulatory obese infertile women. WHAT IS KNOWN ALREADY: Obese women are at increased risk of infertility and are less likely to conceive after infertility treatment. We previously demonstrated that a 6-month lifestyle intervention preceding infertility treatment did not increase the rate of healthy live births (vaginal live birth of a healthy singleton at term) within 24 months of follow-up as compared to prompt infertility treatment in obese infertile women. Natural conceptions occurred more frequently in women who received a 6-month lifestyle intervention preceding infertility treatment. STUDY DESIGN, SIZE, DURATION: This is a secondary analysis of a multicentre RCT (randomized controlled trial), the LIFEstyle study. Between 2009 and 2012, 577 obese infertile women were randomly assigned to a 6-month lifestyle intervention followed by infertility treatment (intervention group) or to prompt infertility treatment (control group). Subgroups were predefined in the study protocol, based on frequently used cut-off values in the literature: age (≥36 or

BACKGROUND: The prevalence of obesity, an important cardiometabolic risk factor, is rising in women. Lifestyle improvements are the first step in treatment of obesity, but the success depends on factors like timing and motivation. Women are especially receptive to advice about lifestyle before and during pregnancy. Therefore, we hypothesize that the pre-pregnancy period provides the perfect window of opportunity to improve cardiometabolic health and quality of life of obese infertile women, by means of a lifestyle intervention.METHODS AND FINDINGS: Between 2009-2012, 577 infertile women between 18 and 39 years of age, with a Body Mass Index of ≥ 29 kg/m2, were randomized to a six month lifestyle intervention preceding infertility treatment, or to direct infertility treatment. The goal of the intervention was 5-10% weight loss or a BMI < 29 kg/m2. Cardiometabolic outcomes included weight, waist- and hip circumference, body mass index, systolic and diastolic blood pressure, fasting glucose and insulin, HOMA-IR, hs-CRP, lipids and metabolic syndrome. All outcomes were measured by research nurses at randomization, 3 and 6 months. Self-reported quality of life was also measured at 12 months. Three participants withdrew their informed consent, and 63 participants discontinued the intervention program. Intention to treat analysis was conducted. Mixed effects regression models analyses were performed. Results are displayed as estimated mean differences between intervention and control group. Weight (-3.1 kg 95% CI: -4.0 to -2.2 kg; P < .001), waist circumference (-2.4 cm 95% CI: -3.6 to -1.1 cm; P < .001), hip circumference (-3.0 95% CI: -4.2 to -1.9 cm; P < .001), BMI (-1.2 kg/m2 95% CI: -1.5 to -0.8 kg/m2; P < .001), systolic blood pressure (-2.8 mmHg 95% CI: -5.0 to -0.7 mmHg; P = .01) and HOMA-IR (-0.5 95% CI: -0.8 to -0.1; P = .01) were lower in the intervention group compared to controls. Hs-CRP and lipids did not differ between groups. The odds ratio for metabolic syndrome in the intervention group was 0.53 (95% CI: 0.33 to 0.85; P < .01) compared to controls. Physical QoL scores were higher in the lifestyle intervention group (2.2 95% CI: 0.9 to 3.5; P = .001) while mental QoL scores did not differ.CONCLUSIONS: In obese infertile women, a lifestyle intervention prior to infertility treatment improves cardiometabolic health and self-reported physical quality of life (LIFEstyle study: Netherlands Trial Register: NTR1530).

Study question Are there treatment selection markers that could aid in identifying couples, with unexplained or mild male subfertility, who would have better chances of a healthy child with IVF with single embryo transfer (IVF-SET) than with IUI with ovarian stimulation (IUI-OS)? Summary answer We did not find any treatment selection markers that were associated with better chances of a healthy child with IVF-SET instead of IUI-OS in couples with unexplained or mild male subfertility. What is known already A recent trial, comparing IVF-SET to IUI-OS, found no evidence of a difference between live birth rates and multiple pregnancy rates. It was suggested that IUI-OS should remain the first-line treatment instead of IVF-SET in couples with unexplained or mild male subfertility and female age between 18 and 38 years. The question remains whether there are some couples that may have higher pregnancy chances if treated with IVF-SET instead of IUI. Study design, size, duration We performed our analyses on data from the INeS trial, where couples with unexplained or mild male subfertility and an unfavourable prognosis for natural conception were randomly allocated to IVF-SET, IVF in a modified natural cycle or IUI-OS. In view of the aim of this study, we only used data of the comparison between IVF-SET (201 couples) and IUI-OS (207 couples). Participants/materials, setting, methods We pre-defined the following baseline characteristics as potential treatment selection markers: female age, ethnicity, smoking status, type of subfertility (primary/secondary), duration of subfertility, BMI, pre-wash total motile count and Hunault prediction score. For each potential treatment selection marker, we explored the association with the chances of a healthy child after IVF-SET and IUI-OS and tested if there was an interaction with treatment. Given the exploratory nature of our analysis, we used a P-value of 0.1. Main results and the role of chance None of the markers were associated with higher chances of a healthy child from IVF-SET compared to IUI-OS (P-value for interaction >0.10). Limitations, reasons for caution Since this is the first large study that looked at potential treatment selection markers for IVF-SET compared to IUI-OS, we had no data on which to base a power calculation. The sample size was limited, making it difficult to detect any smaller associations. Wider implications of the findings We could not identify couples with unexplained or mild male subfertility who would have had higher chances of a healthy child from immediate IVF-SET than from IUI-OS. As in the original trial IUI-OS had similar effectiveness and was less costly compared to IVF-SET, IUI-OS should remain the preferred first-line treatment in these couples. Study funding/competing interest(s) The study was supported by a grant from the Netherlands Organization for Health Research and Development, and a grant from the Netherlands' association of health care insurers. There are no conflicts of interest. Trial registration number The trial was registered at the Dutch trial registry (NTR939).

Study question What is the feasibility of performing transvaginal hydrolaparoscopy (THL) in an outpatient setting? Summary answer It is feasible to perform THL in an outpatient setting, reflected by a low complication and failure rate and a high patients' satisfaction. What is known already THL is a safe method to investigate tubal patency and exploring the pelvis in subfertile women. Study design, size, duration Retrospective cohort study of 1127 subfertile women who underwent THL as primary diagnostic method for testing tubal patency in an outpatient setting. Participants/materials, setting, methods We studied all THL procedures performed as a primary diagnostic tubal patency test in an outpatient setting in subfertile women starting from the initial THL in four large hospitals. Baseline characteristics were obtained, as well as the outcome of the procedures in terms of success, complications and findings by examining medical records. We used a uniform visual analogue scale (VAS) score document to collect data on pain and acceptability prospectively and compared two methods of pain relief. Main results and the role of chance We studied a total of 1103 women who underwent THL. Successful access to the pouch of Douglas was achieved in 1028 women (93.2%), and 1017 women had a complete evaluation (92.2%). Double-sided tubal patency was found in 844 women (83%), unilateral tubal patency in 127 women (12.5%), while in 46 women (4.5%) bilateral occluded tubes were diagnosed. Endometriosis alone was seen in 64 women (6.3%), adhesions alone in 87 women (8.6%) and both endometriosis and adhesions in 42 women (4.1%).Complications occurred in 29 (2.6%) women, including 10 perforations of the rectum (0.9%), 8 perforations of the posterior uterine wall (0.7%) and 5 infections/pelvic inflammatory diseases (PIDs) (0.5%). Bleeding of the vaginal wall requiring intervention and hospital admissions due to pain was seen in 4 (0.4%) and 2 women, respectively (0.2%). The average pain score was rated 4.0 (±2.4 SD) on a VAS from 0 to 10 with 0 meaning no pain at all with no difference in different types of pain relief. Acceptability was rated 1.5 (±2.1 SD). Limitations, reasons for caution The main limitation of the study is its retrospective character and the fact that only a fourth of the women were asked for pain and acceptability scores. Wider implications of the findings THL can be used as a primary method for tubal assessment in an outpatient setting. Further randomized studies are needed to assess whether THL is superior to other methods and strategies for tubal assessment in terms of prognostic capacity and cost-effectiveness. Study funding/competing interest No external funding was either sought or obtained for this study. The authors have no competing interests to declare.

BACKGROUNDSmall lifestyle-intervention studies suggest that modest weight loss increases the chance of conception and may improve perinatal outcomes, but large randomized, controlled trials are lacking.METHODSWe randomly assigned infertile women with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 29 or higher to a 6-month lifestyle intervention preceding treatment for infertility or to prompt treatment for infertility. The primary outcome was the vaginal birth of a healthy singleton at term within 24 months after randomization. RESULTS We assigned women who did not conceive naturally to one of two treatment strategies: 290 women were assigned to a 6-month lifestyle-intervention program preceding 18 months of infertility treatment (intervention group) and 287 were assigned to prompt infertility treatment for 24 months (control group). A total of 3 women withdrew consent, so 289 women in the intervention group and 285 women in the control group were included in the analysis. The discontinuation rate in the intervention group was 21.8%. In intention-to-treat analyses, the mean weight loss was 4.4 kg in the intervention group and 1.1 kg in the control group (PCONCLUSIONSIn obese infertile women, a lifestyle intervention preceding infertility treatment, as compared with prompt infertility treatment, did not result in higher rates of a vaginal birth of a healthy singleton at term within 24 months after randomization. (Funded by the Netherlands Organization for Health Research and Development; Netherlands Trial Register number, NTR1530.)

STUDY QUESTION: What is the cost-effectiveness of in vitro fertilization(IVF) with conventional ovarian stimulation, single embryotransfer (SET) and subsequent cryocycles or IVF in a modified natural cycle (MNC) compared with intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH) as a first-line treatment in couples with unexplained subfertility and an unfavourable prognosis on natural conception?.SUMMARY ANSWER: Both IVF strategies are significantly more expensive when compared with IUI-COH, without being significantly more effective. In the comparison between IVF-MNC and IUI-COH, the latter is the dominant strategy. Whether IVF-SET is cost-effective depends on society's willingness to pay for an additional healthy child.WHAT IS KNOWN ALREADY: IUI-COH and IVF, either after conventional ovarian stimulation or in a MNC, are used as first-line treatments for couples with unexplained or mild male subfertility. As IUI-COH is less invasive, this treatment is usually offered before proceeding to IVF. Yet, as conventional IVF with SET may lead to higher pregnancy rates in fewer cycles for a lower multiple pregnancy rate, some have argued to start with IVF instead of IUI-COH. In addition, IVF in the MNC is considered to be a more patient friendly and less costly form of IVF.STUDY DESIGN, SIZE, DURATION: We performed a cost-effectiveness analysis alongside a randomized noninferiority trial. Between January 2009 and February 2012, 602 couples with unexplained infertility and a poor prognosis on natural conception were allocated to three cycles of IVF-SET including frozen embryo transfers, six cycles of IVF-MNC or six cycles of IUI-COH. These couples were followed until 12 months after randomization.PARTICIPANTS/MATERIALS, SETTING, METHODS: We collected data on resource use related to treatment, medication and pregnancy from the case report forms. We calculated unit costs from various sources. For each of the three strategies, we calculated the mean costs and effectiveness. Incremental cost-effectiveness ratios (ICER) were calculated for IVF-SET compared with IUI-COH and for IVF-MNC compared with IUI-COH. Nonparametric bootstrap resampling was used to investigate the effect of uncertainty in our estimates.MAIN RESULTS AND THE ROLE OF CHANCE: There were 104 healthy children (52%) born in the IVF-SET group, 83 (43%) the IVF-MNC group and 97 (47%) in the IUI-COH group. The mean costs per couple were (sic)7187 for IVF-SET, (sic)8206 for IVF-MNC and (sic)5070 for IUI-COH. Compared with IUI-COH, the costs for IVF-SET and IVF-MNC were significantly higher (mean differences (sic)2117; 95% CI: (sic)1544-(sic)2657 and (sic)3136, 95% CI: (sic)2519-(sic)3754, respectively). The ICER for IVF-SET compared with IUI-COH was (sic)43 375 for the birth of an additional healthy child. In the comparison of IVF-MNC to IUI-COH, the latter was the dominant strategy, i.e. more effective at lower costs.LIMITATIONS, REASONS FOR CAUTION: We only report on direct health care costs. The present analysis is limited to 12 months.WIDER IMPLICATIONS OF THE FINDINGS: Since we found no evidence in support of offering IVF as a first-line strategy in couples with unexplained and mild subfertility, IUI-COH should remain the treatment of first choice.

Objectives: To compare the effectiveness of in vitro fertilisation with single embryo transfer or in vitro fertilisation in a modified natural cycle with that of intrauterine insemination with controlled ovarian hyperstimulation in terms of a healthy child. Design: Multicentre, open label, three arm, parallel group, randomised controlled non-inferiority trial. Setting: 17 centres in the Netherlands. Participants: Couples seeking fertility treatment after at least 12 months of unprotected intercourse, with the female partner aged between 18 and 38 years, an unfavourable prognosis for natural conception, and a diagnosis of unexplained or mild male subfertility. Interventions: Three cycles of in vitro fertilisation with single embryo transfer (plus subsequent cryocycles), six cycles of in vitro fertilisation in a modified natural cycle, or six cycles of intrauterine insemination with ovarian hyperstimulation within 12 months after randomisation. Main outcome measures: The primary outcome was birth of a healthy child resulting from a singleton pregnancy conceived within 12 months after randomisation. Secondary outcomes were live birth, clinical pregnancy, ongoing pregnancy, multiple pregnancy, time to pregnancy, complications of pregnancy, and neonatal morbidity and mortality Results: 602 couples were randomly assigned between January 2009 and February 2012; 201 were allocated to in vitro fertilisation with single embryo transfer, 194 to in vitro fertilisation in a modified natural cycle, and 207 to intrauterine insemination with controlled ovarian hyperstimulation. Birth of a healthy child occurred in 104 (52%) couples in the in vitro fertilisation with single embryo transfer group, 83 (43%) in the in vitro fertilisation in a modified natural cycle group, and 97 (47%) in the intrauterine insemination with controlled ovarian hyperstimulation group. This corresponds to a risk, relative to intrauterine insemination with ovarian hyperstimulation, of 1.10 (95% confidence interval 0.91 to 1.34) for in vitro fertilisation with single embryo transfer and 0.91 (0.73 to 1.14) for in vitro fertilisation in a modified natural cycle. These 95% confidence intervals do not extend below the predefined threshold of 0.69 for inferiority. Multiple pregnancy rates per ongoing pregnancy were 6% (7/121) after in vitro fertilisation with single embryo transfer, 5% (5/102) after in vitro fertilisation in a modified natural cycle, and 7% (8/119) after intrauterine insemination with ovarian hyperstimulation (one sided P=0.52 for in vitro fertilisation with single embryo transfer compared with intrauterine insemination with ovarian hyperstimulation; one sided P=0.33 for in vitro fertilisation in a modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation). Conclusions: In vitro fertilisation with single embryo transfer and in vitro fertilisation in a modified natural cycle were non-inferior to intrauterine insemination with controlled ovarian hyperstimulation in terms of the birth of a healthy child and showed comparable, low multiple pregnancy rates. Trial registration: Current Controlled Trials ISRCTN52843371; Nederlands Trial Register NTR939.

Item does not contain fulltext OBJECTIVE: To assess the impact of elevated early follicular progesterone (P) levels in gonadotropin-releasing hormone (GnRH) antagonist cycles on clinical outcome using prospective data in combination with a systematic review and meta-analysis. DESIGN: Nested study within a multicenter randomized controlled trial and a systematic review and meta-analysis. SETTING: Reproductive medicine center in an university hospital. PATIENT(S): 158 in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) patients. INTERVENTION(S): Recombinant follicle-stimulating hormone (FSH) (150-225 IU) administered daily from cycle day 2 onward; GnRH antagonist treatment randomly started on cycle day 2 or 6; assignment into two groups according to P level on cycle day 2: normal or elevated (>4.77 nmol/L or >1.5 ng/mL, respectively). MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate (OPR) per started cycle. RESULT(S): The incidence of elevated P was 13.3%. A non-statistically-significant difference in OPR was present between the normal and elevated P groups (27.0% vs. 19.0%). No differential impact of early or late GnRH antagonist initiation on the effect of elevated or normal P on OPR was observed. A systematic search of Medline and EMBASE from 1972-2013 was performed to identify studies analyzing elevated early P levels in GnRH antagonists. The meta-analysis (n=1,052) demonstrated that elevated P levels statistically significantly decreased the OPR with 15% (95% CI -23, -7 %). Heterogeneity across the studies, presumably based on varying protocols, may have modulated the effect of elevated P. CONCLUSION(S): From the present meta-analysis it appears that early elevated P levels are associated with a lower OPR in GnRH antagonists. The incidence of such a condition, however, is low. CLINICAL TRIAL REGISTRATION NUMBER: NCT00866034.

Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) play an important role in regulating follicle growth and maturation. We have evaluated whether responsiveness to gonadotrophins during an in-vitro fertilization (IVF) treatment is related to follicular fluid IGF-I and IGFBP-3 concentrations. We also investigated if a difference is present in IGF-I and IGFBP-3 concentrations between patients treated with human menopausal gonadotrophin (HMG) and patients treated with highly purified follicle stimulating hormone (FSH). We have measured IGF-I and IGFBP-3 in follicular fluid from pre-ovulatory follicles in an IVF programme. All 70 patients were stimulated after being down-regulated with a gonadotrophin-releasing hormone (GnRH) analogue. IGF-I concentrations in follicular fluid were significantly inversely correlated with the number of ampoules FSH administered and number of days of FSH administration, and significantly correlated with the number of follicles aspirated. IGFBP-3 concentrations were not correlated with any other parameter measured nor were IGF-I and IGFBP-3 concentrations correlated. IGFBP-3 concentrations were significantly higher in patients receiving highly purified FSH compared with patients receiving HMG (P < 0.005). These results are new evidence that IGF-I concentration in follicular fluid is higher in women who respond better to follicular stimulation, i.e. women who grow many follicles, women who need a shorter duration of stimulation and women who need fewer ampoules FSH before oocyte retrieval.

study question: what is the impact of initiating GnRH antagonist co-treatment for in vitro fertilization (IVF) on cycle day (CD) 2 compared with CD 6 on live birth rate (LBR) per started cycle and on the cumulative live birth rate (CLBR)? Summary answer: early initiation of GnRH antagonist does not appear to improve clinical outcomes of IVF compared with midfollicular initiation. What is known already: during ovarian stimulation for IVF, GnRH antagonist co-treatment is usually administered from the midfollicular phase onwards. Earlier initiation may improve the follicular phase hormonal milieu and therefore overall clinical outcomes. Study design, size, duration: this open-label, multicentre randomized controlled trial was conducted between September 2009 and July 2011. A web-based program was used for randomization and 617 IVF-intracytoplasmic sperm injection (ICSI) patients were included. Participants/materials, setting, methods: recombinant FSH (150–225 IU) was administered daily from CD 2 onwards in both groups. The study group (CD2; n = 308) started GnRH antagonist co-treatment on CD 2, whereas the control group (CD6; n = 309) started on CD 6. Main results and the role of chance: there were no significant differences in clinical outcomes between the two groups. A non-significant trend towards a higher LBR per started cycle and CLBR was observed in the CD6 group compared with the CD2 group (LBR: 24.0 versus 21.5%, P = 0.5; CLBR: 29.9 versus 26.7%, P = 0.6). Limitations, reasons for caution: the study was terminated prematurely because no significant difference was observed in clinical outcomes after 617 inclusions. A much larger study population would be needed to detect a small significant difference in favour of either study arm, which raises the question of whether this would be relevant for clinical practice. Wider implications of the findings: the present study shows that the additional treatment burden and costs of starting GnRH antagonist on CD 2 instead of on CD 6 are not justified, as early initiation of GnRH antagonist does not improve LBRs. Study funding/competing interests: this study was partially supported by a grant from Merck Serono. O.H., M.J.C.E, A.V., P.A.D., R.E.B., G.J.E.O., C.A.G.H., G.C.D.M., H.J.V., P.F.M.H. and A.B. have nothing to declare. F.J.B. has received fees and grant support from the following companies (in alphabetic order): Ferring, Gedeon Richter, Merck Serono, MSD and Roche. B.J.C. has received fees and grant support from the following companies (in alphabetic order): Ferring, Merck Serono and MSD. C.B.L has received fees and grant support from the following companies (in alphabetic order): Auxogen, Ferring, Merck Serono and MSD. B.C.J.M.F. has received fees and grant support from the following companies (in alphabetic order): Andromed, Ardana, Ferring, Genovum, Merck Serono, MSD, Organon, Pantharei Bioscience, PregLem, Schering, Schering Plough, Serono and Wyeth. J.S.E.L. has received fees and grant support from the following companies (in alphabetic order): Ferring, Gennovum, MSD, Merck Serono, Organon, Schering Plough and Serono. N.S.M. has received fees and grant support from the following companies (in alphabetic order): Anecova, Ferring, Merck Serono, MSD, Organon and Serono

We investigated whether the hypo-osmotic swelling (HOS) test is a reliable screening method for routine semen specimen quality screening. Of 159 male patients, 171 semen samples were investigated using the HOS test as well as routine semen specimen screening used in our clinic. There was a significant correlation between the HOS test and most semen parameters. There was no significant correlation between the HOS test and the percentage of morphologically normal spermatozoa in the initial semen sample. The HOS test is a reliable screening method for routine semen quality screening. © 1996 Wiley-Liss, Inc.

BACKGROUND Laparoscopic electrocautery of the ovaries and ovulation induction with gonadotrophins are both second line treatments for women with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). Long-term follow-up after electrocautery versus ovulation induction with gonadotrophins has demonstrated at least comparable chances for a first live born child with a reduced need for ovulation induction or assisted reproduction treatment and increased chances for a second live born child. In this study, we report on the long-term economic consequences of both treatment modalities. METHODS Between February 1998 and October 2001, we performed a multi-centre randomized controlled trial (RCT) comparing a strategy of laparoscopic electrocautery of the ovaries, followed by clomiphene citrate and gonadotrophins when anovulation persisted, and a strategy of ovulation induction with gonadotrophins in women with clomiphene citrate-resistant PCOS. Eight to twelve years after randomization we performed a follow-up study on reproductive outcome in these women and the fertility treatments they had needed including data on direct medical costs of pregnancy and delivery. Clinical data included number of treatment cycles, live births, miscarriages, ectopic pregnancies and multiple pregnancies. We calculated mean costs per woman after randomization until the first live birth. Confidence intervals (CIs) were estimated by bootstrapping. RESULTS We obtained data for an economic analysis on 159 of the 168 randomized women (95%). In total, 71 of 83 women (86%) allocated to the electrocautery strategy and 69 of 85 women (81%) allocated to the gonadotrophin strategy had at least one live birth. Given the equivalence between the two treatment strategies in terms of a first live birth-the primary outcome measure-our analysis focused on the cost difference between the two strategies within a mean follow-up time of 8-12 years. The mean costs per first live birth after randomization were €11 176 (95% CI: €9689-€12 549) for the electrocautery group and €14 423 (95% CI: €12 239-€16 606) for the recombinant FSH group, resulting in significantly lower costs (P < 0.05) per first live birth for women allocated to the electrocautery group (mean difference €3247; 95% CI: €650-€5814). CONCLUSION In women with clomiphene-resistant PCOS, laparoscopic electrocautery of the ovaries results in significantly lower costs per live birth than ovulation induction with gonadotrophins for an at least equal effectiveness.

The study was designed to compare the follow-up results after laser and cold-knife conisation. In both groups 28 patients were included matched for age and parity. All had histologically verified cervical intraepithelial neoplasia (CIN) 3. Laser conisation was performed using a CO2 laser attached to a handpiece. The same surgeon treated all patients. Follow-up consisted of cytology and colposcopy after 3, 12, 24, 36, 48 and 60 months. There were no intra- or postoperative complications. Recurrence or residual disease was found in 7% in both groups. In the laser group, in six patients the histological interpretation of extension of CIN in the excision margin was not reliable, compared to one case in the cold-knife group. The number of inconclusive colposcopy in the laser group is one out of 26 compared to the cold-knife group 17 out of 24 after 60 months. The major advantage of using a CO2 laser for conisation of the cervix in cases of CIN is the reliability of the colposcopic examination.

Publisher Summary This chapter discusses the tests commonly used to assess ovarian function in infertility patients, as well as some experimental tests. The success of an assisted reproduction treatment is defined as pregnancy rate, ongoing pregnancy rate, and the ultimate goal of assisted reproduction, live birth of a baby. The chance of a spontaneous conception as well as the prognosis of infertility therapy can only be determined when there is some knowledge about the remaining capacity for reproduction. The first functional test used on all couples attending a fertility clinic is age of the woman. Basal hormone levels—such as—FSH, estradiol, and progesterone are measured, which is the most widely used invasive test to measure ovarian reserve. The most useful markers for a successful outcome of assisted reproduction are those that can be assessed before the treatment begins. The function of the pituitary–ovarian axis is also determined. Biochemical markers in follicular fluid could be used to select those oocytes with optimal quality for transfer. The quality of embryos is also determined by embryo quality scoring and embryo culture media. The granulose cells and hormone levels after embryo transplant are also considered.