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Research Question: What is the risk of hypogonadism in men with obstructive azoospermia, non-obstructive azoospermia (NOA) or Klinefelter syndrome after testicular sperm extraction (TESE)?, Design: This prospective longitudinal cohort study was carried out between 2007 and 2015., Results: Around 36% of men with Klinefelter syndrome, 4% of men with obstructive azoospermia and 3% of men with NOA needed testosterone replacement therapy (TRT). Klinefelter syndrome was strongly associated with TRT while no association was found between obstructive azoospermia or NOA and TRT. Irrespective of the pre-operative diagnosis, a higher testosterone concentration before TESE was associated with a lower chance of needing TRT., Conclusions: Men with obstructive azoospermia or NOA have a similar moderate risk of clinical hypogonadism after TESE, while this risk is much larger for men with Klinefelter syndrome. The risk of clinical hypogonadism is lower when testosterone concentrations are high before TESE., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Research Question: How do hospitals with and without an early pregnancy assessment unit (EPAU) adhere to guideline-based quality indicators for an EPAU relating to logistics, access to services and quality of early pregnancy care?, Design: A qualitative interview study assessing the adherence to 19 quality indicators in four hospitals with an EPAU and four hospitals without an EPAU in the Netherlands. For each quality indicator, a ratio for guideline adherence was calculated. Overall non-adherence per hospital was defined as less than 100% adherence to the 19 quality indicators., Results: Non-adherence was seen in three indicators (3/19 [16%]) for hospitals with an EPAU and in five indicators (5/19 [26%]) for hospitals without an EPAU. A standard digital system for the registration of ultrasound findings and clear explanation of all treatment options was present in all hospitals with an EPAU and in three hospitals without an EPAU. Certified ultrasound training for working staff members was absent in all hospitals. A discrete waiting area was present in one hospital with an EPAU compared with none of the hospitals without an EPAU. Self-referrals from women with a previous ectopic pregnancy was accepted in one hospital with and in one hospital without an EPAU., Conclusions: Non-adherence to guideline-based quality indicators for an EPAU was about the same for hospitals with and without an EPAU in the Netherlands., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Research Question: Are unmet needs for psychosocial counselling, peer support and friends/family support in parents directly and/or indirectly related to the mental health of parents and their donor-children?, Design: A cross-sectional sample of 214 parents participated in this quantitative study via an online questionnaire. The sample comprised mothers and fathers in a heterosexual relationship (n = 85), mothers in a lesbian relationship (n = 67) and single mothers (n = 62). Parents were recruited via three Dutch fertility clinics and four network organizations. Unmet support needs were measured with an adapted version of the Unmet Needs for Parenting Support questionnaire, changing the original items into items about donor conception. The items were derived from a qualitative study and checked by experts in donor conception. The parents' mental health was measured with the Adult Self Report and the donor-children's mental health with the Child Behaviour Checklist. A multigroup mediation analysis was conducted to explore relationships between parents' unmet support needs and their child's mental health, with the parents' mental health as a possible mediator., Results: There were no direct relations between parents' unmet support needs and the mental health of donor-children. Unmet needs for psychosocial counselling, peer support and friends/family support for parents and children's mental health were indirectly related through the mental health of the parents: 0.074 (CI 95%  = 0.013-0.136; P = 0.017), 0.085 (CI 95% = 0.018-0.151; P = 0.036) and 0.063 (CI 95% = 0.019-0.106; P = 0.013), respectively., Conclusions: We recommend that fertility clinics, network organizations and authorities for infertility counsellors make their support available to parents for extended periods after their treatment. Further qualitative studies are necessary to assess how to relieve unmet support needs during donor sperm treatment., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Research Question: What are the unmet needs after psychosocial counselling and mental health of women who opt for donor sperm treatment (DST), and are unmet counselling needs related to their mental health?, Design: This quantitative study included women in a heterosexual relationship (n = 19), women in a lesbian relationship (n = 25) and single women (n = 51) who opted for DST. Women were included if they had passed the DST intake procedure at a Dutch fertility clinic, were not pregnant and had no previous donor-child. Unmet needs were measured by a self-developed questionnaire based on specific topics identified in a previous qualitative study with added items from experts in the field of DST. The Adult Self Report was used to measure mental health. Relationships between unmet counselling needs and mental health were explored by multiple regression analyses., Results: Fifty-two women (55%) reported unmet counselling needs. Women in heterosexual relationships mostly had unmet counselling needs on the topics of the decision to opt for DST (n = 11, 58%) and non-genetic parenthood (n = 11, 58%); women in lesbian relationships (n = 10, 40%) and single women (n = 14, 27%) mostly had unmet needs on the topic of choosing a sperm donor. In general, women had good mental health, but 13 (14%) met the criteria for clinical mental health problems. Women with more unmet counselling needs also had more mental health problems., Conclusions: Evidence-based guidelines for psychosocial counselling in DST should be developed. Only then can counselling be improved and be fit for purpose., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Research Question: Women who face age-related fertility decline have the option to safeguard future reproductive potential by banking oocytes or ovarian tissue. What are the methods that women prefer and what factors are important in their decision-making?, Design: Qualitative interview study, participants were recruited through monthly information sessions at a university hospital on oocyte banking, postings on social media, websites and newsletters and snowball sampling. Women had to be aged 35 years or older, single, childless and with a possible future desire for motherhood. Key concepts of the Health Belief Model were used as framework for the analyses., Results: In total, 15 women participated in this qualitative study. For oocyte banking, they mentioned chances of success, extra time and faith in the technique and healthcare professionals as benefits. Risks for themselves or future children and costs were considered to be barriers in decision making. For ovarian tissue banking, the chances of success, the possibility of natural conception, the time investment and effect on menopausal symptoms were seen as benefits, and lack of experience and lack of information were considered barriers for themselves or their future children. Overall, they considered the procedures involved in oocyte banking as relatively 'easy', whereas ovarian tissue banking was seen as a more invasive procedure., Conclusion: Most women preferred oocyte banking over ovarian tissue banking because of its relative convenience. Future quantitative research in a larger cohort is necessary to confirm the findings and provide more insight into the relative importance of the different factors influencing women's decision., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Research Question: What valid guideline-based quality indicators can measure quality of care in early pregnancy assessment units (EPAU)?, Design: The systematic RAND-modified Delphi method was used to develop an indicator set from four evidence-based guidelines. An international expert panel was assembled to extract recommendations from these guidelines to establish quality indicators., Results: A total of 119 recommendations were extracted. Eleven recommendations received a high median score and top five score above the 75th percentile and were selected as key recommendations. The expert panel reassessed 15 high score recommendations and top five score between the 50th and 75th percentile as well as one high score recommendation without consensus. Eight of these 16 recommendations were selected in the second round as key recommendations. The key recommendations were formulated into a set of 19 quality indicators, summarized as follows: women referred to an EPAU could be seen within 24 h and receive a clear explanation on treatment options; designated senior staff members could be responsible for the unit and staff could have had ultrasound training; protocols could be available for daily practice covering all treatment options for miscarriage and ectopic pregnancy; and an EPAU could have access to urine pregnancy testing and serum HCG assays., Conclusions: Nineteen quality indicators to measure early pregnancy care provided by EPAU were identified., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: What is the cost-effectiveness of gonadotrophins compared with clomiphene citrate in couples with unexplained subfertility undergoing intrauterine insemination (IUI) with ovarian stimulation under strict cancellation criteria?, Design: A cost-effectiveness analysis alongside a randomized controlled trial (RCT). Between July 2013 and March 2016, 738 couples were randomized to gonadotrophins (369) or clomiphene citrate (369) in a multicentre RCT in the Netherlands. The direct medical costs of both strategies were compared. Direct medical costs included costs of medication, cycle monitoring, insemination and, if applicable, pregnancy monitoring. Non-parametric bootstrap resampling was used to investigate the effect of uncertainty in estimates. The cost-effectiveness analysis was performed according to intention-to-treat. The incremental cost-effectiveness ratio (ICER) between gonadotrophins and clomiphene citrate for ongoing pregnancy and live birth was assessed., Results: The mean costs per couple were €1534 for gonadotrophins and €1067 for clomiphene citrate (mean difference of €468; 95% confidence interval [CI] €464-472). As ongoing pregnancy rates were 31% in women allocated to gonadotrophins and 26% in women allocated to clomiphene citrate (relative risk 1.16, 95% CI 0.93-1.47), the ICER was €21,804 (95% CI €11,628-31,980) per additional ongoing pregnancy with gonadotrophins and €17,044 (95% CI €8998-25,090) per additional live birth with gonadotrophins., Conclusions: Gonadotrophins are more expensive compared with clomiphene citrate in couples with unexplained subfertility undergoing IUI with adherence to strict cancellation criteria, without being significantly more effective., (Copyright © 2019. Published by Elsevier Ltd.)

Research Question: Can women be identified, on the basis of baseline patient characteristics, as having better chances of an ongoing pregnancy with FSH instead of clomiphene citrate as stimulation agent in intrauterine insemination for unexplained subfertility?, Design: A secondary analysis of a multicentre randomized controlled superiority trial; the SUPER study. Between July 2013 and March 2016, couples with unexplained subfertility undergoing intrauterine inemination (IUI) were allocated to an FSH or clomiphene citrate group. Female age, body mass index, duration of subfertility, primary versus secondary subfertility, antral follicle count and total motile count were assessed. For each of these factors, a logistic regression model was developed to assess if different estimated effects of FSH versus clomiphene citrate on ongoing pregnancy occurred within strata of each factor., Results: A total of 684 couples received 2259 IUI cycles; 338 couples were allocated to FSH, of which 84 conceived leading to ongoing pregnancy and 346 couples were allocated to clomiphene citrate, of which 71 conceived leading to ongoing pregnancy. None of the treatment selection markers was associated with better ongoing pregnancy chances after IUI with FSH compared with clomiphene citrate., Conclusion: In couples with unexplained subfertility undergoing IUI, no baseline treatment selection markers could be identified to determine whether ovaries should be stimulated with FSH or clomiphene citrate., (Copyright © 2019 Reproductive Healthcare Ltd. All rights reserved.)

Research Question: Hysterosalpingography (HSG) with an oil-based contrast has been shown to increase ongoing pregnancy rates compared with HSG with water-based contrast, but it remains unclear if an effect of HSG occurs compared with no HSG., Design: A secondary data-analysis of a prospective cohort study among 4556 couples that presented with unexplained subfertility in 38 clinics in the Netherlands between January 2002 and December 2004. A time-varying Cox regression with inverse probability of treatment weighing was used to analyse ongoing pregnancy rates in women after undergoing the HSG procedure (with the use of either water- or oil-based contrast media) compared with women who did not undergo HSG., Results: The probability of natural conception within 24 months after first presentation at the fertility clinic was increased after HSG, regardless of the type of contrast medium used, compared with no HSG (adjusted hazard ratio 1.48, 95% CI 1.26 to 1.73, corresponding to an absolute increase in 6-month pregnancy rate of +6%). When this analysis was limited to HSGs that were made with water-contrast, the treatment effect remained (adjusted hazard ratio 1.40, 95% CI 1.16 to 1.70)., Conclusions: HSG increases the ongoing pregnancy rate of couples with unexplained subfertility compared with no HSG, regardless of the contrast medium used. Results need to be validated in future, preferably randomized, studies., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: What are the reproductive outcomes of women who bank oocytes for fertility preservation?, Design: A prospective follow-up study of a cohort of 327 women who banked their oocytes for fertility preservation was carried out between July 2009 and August 2015. The indications for oocyte banking and outcomes of ovarian stimulation were collected from medical files. Follow-up data were obtained from an additional questionnaire., Results: In total, 243 out of 327 women (74%) responded and 228 women (70%) consented to participate and returned the questionnaire. The median time to follow-up of these women was 31 months. A total of 101 women (44%) were trying, or had tried, to become pregnant after oocyte banking, of which 66 became pregnant (65%). Five women reported an unintended pregnancy. Of these, 71 women became pregnant, 76% conceived naturally, 7% through intracytoplasmic sperm injection with their vitrified-warmed oocytes and 17% by other medically assisted reproduction treatments. Six women attempted to achieve a pregnancy using their banked oocytes. Of the six pregnancies achieved in five women, two resulted in a live birth. A total of thirty-eight women reported a live birth at the time of follow-up., Conclusion: Oocyte banking can be considered a form of risk management or preventive medicine because it is not certain that the women will experience sterility in the future., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: In many countries, clomifene citrate is the treatment of first choice in women with normogonadotropic anovulation (ie, absent or irregular ovulation). If these women ovulate but do not conceive after several cycles with clomifene citrate, medication is usually switched to gonadotrophins, with or without intrauterine insemination. We aimed to assess whether switching to gonadotrophins is more effective than continuing clomifene citrate, and whether intrauterine insemination is more effective than intercourse., Methods: In this two-by-two factorial multicentre randomised clinical trial, we recruited women aged 18 years and older with normogonadotropic anovulation not pregnant after six ovulatory cycles of clomifene citrate (maximum of 150 mg daily for 5 days) from 48 Dutch hospitals. Women were randomly assigned using a central password-protected internet-based randomisation programme to receive six cycles with gonadotrophins plus intrauterine insemination, six cycles with gonadotrophins plus intercourse, six cycles with clomifene citrate plus intrauterine insemination, or six cycles with clomifene citrate plus intercourse. Clomifene citrate dosages varied from 50 to 150 mg daily orally and gonadotrophin starting dose was 50 or 75 IU daily subcutaneously. The primary outcome was conception leading to livebirth within 8 months after randomisation defined as any baby born alive after a gestational age beyond 24 weeks. Primary analysis was by intention to treat. We made two comparisons, one in which gonadotrophins were compared with clomifene citrate and one in which intrauterine insemination was compared with intercourse. This completed study is registered with the Netherlands Trial Register, number NTR1449., Findings: Between Dec 8, 2008, and Dec 16, 2015, we randomly assigned 666 women to gonadotrophins and intrauterine insemination (n=166), gonadotrophins and intercourse (n=165), clomifene citrate and intrauterine insemination (n=163), or clomifene citrate and intercourse (n=172). Women allocated to gonadotrophins had more livebirths than those allocated to clomifene citrate (167 [52%] of 327 women vs 138 [41%] of 334 women, relative risk [RR] 1·24 [95% CI 1·05-1·46]; p=0·0124). Addition of intrauterine insemination did not increase livebirths compared with intercourse (161 [49%] vs 144 [43%], RR 1·14 [95% CI 0·97-1·35]; p=0·1152). Multiple pregnancy rates for the two comparisons were low and not different. There were three adverse events: one child with congenital abnormalities and one stillbirth in two women treated with clomifene citrate, and one immature delivery due to cervical insufficiency in a woman treated with gonadotrophins., Interpretation: In women with normogonadotropic anovulation and clomifene citrate failure, a switch of treatment to gonadotrophins increased the chance of livebirth over treatment with clomifene citrate; there was no evidence that addition of intrauterine insemination does so., Funding: The Netherlands Organization for Health Research and Development., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Chemotherapy for breast cancer may have a negative impact on reproductive function due to gonadotoxicity. Fertility preservation via banking of oocytes or embryos after ovarian stimulation with FSH can increase the likelihood of a future live birth. It has been hypothesized that elevated serum estrogen levels during ovarian stimulation may induce breast tumour growth. This has led to the use of alternative stimulation protocols with addition of tamoxifen or letrozole. The effectiveness of these stimulation protocols in terms of oocyte yield is unknown., Methods/design: Randomized open-label trial comparing ovarian stimulation plus tamoxifen and ovarian stimulation plus letrozole with standard ovarian stimulation in the course of fertility preservation. The study population consists of women with breast cancer who opt for banking of oocytes or embryos, aged 18-43years at randomisation. Primary outcome is the number of oocytes retrieved at follicle aspiration. Secondary outcomes are number of mature oocytes retrieved, number of oocytes or embryos banked and peak E2 levels during ovarian stimulation., Discussion: Concerning the lack of evidence on which stimulation protocol should be used in women with breast cancer and the growing demand for fertility preservation, there is an urgent need to undertake this study. By performing this study, we will be able to closely monitor the effects of various stimulation protocols in women with breast cancer and pave the way for long term follow up on the safety of this procedure in terms of breast cancer prognosis., Trial Registration: NTR4108., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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 (20%). All predictors of the Hunault model were selected into the revised model plus an additional seven (woman'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 (95% CI 0.69 to 0.73) compared with 0.59 (95% CI 0.57 to 0.61)., (Copyright © 2017. Published by Elsevier Ltd.)

Trials assessing effectiveness in medically assisted reproduction (MAR) should aim to study the desired effect over multiple cycles, as this reflects clinical practice and captures the relevant perspective for the couple. The aim of this study was to assess the extent to which multiple cycles are reported in MAR trials. A sample of randomized controlled trials (RCT) was collected on MAR, published in four time periods, in 11 pre-specified peer-reviewed journals; 253 trials were included: 196 on IVF, 37 on intrauterine insemination and 20 on ovulation induction. Forty-eight (19%) reported on multiple cycles, which was significantly more common in trials on intrauterine insemination and ovulation induction compared with trials on IVF (P < 0.01). Both trials on IVF were multi-centre trials, and those using live birth as primary outcome, reported significantly more often on multiple cycles (OR 3.7 CI 1.1 to 12.5) and (OR 8.7 CI 1.8 to 40.3), respectively. Trials designed to compare protocol variations reported multiple cycles less often (OR 0.07 CI 0.01 to 0.74). Most RCT on MAR, especially those on IVF, do not report cumulative pregnancy rates. As not all women become pregnant in their first cycle, the clinical significance of these trials is limited., (Copyright © 2016 Reproductive Healthcare Ltd. All rights reserved.)

In this observational study, the effect of the introduction of the first Early Pregnancy Assessment Unit (EPAU) in a university hospital in The Netherlands in 2008 on early pregnancy care is analysed. Derivatives of quality of care were measured before and after the establishment of the EPAU, with the aim of reducing unnecessary care. Care within three time periods was measured: 2006, 2009 and 2012. In 2006, 14% of women who had experienced a miscarriage were admitted to the hospital, whereas in 2009 and 2012 no women were admitted. The surgical management rate for miscarriage decreased from 79% (2006) to 6% (2009) and 28% (2012). Karyotyping of couples who had experienced recurrent miscarriage decreased from 100% (2006) to 17% (2009) and 33% (2012). The surgical management rate for ectopic pregnancy decreased from 50% (2006) to 25% (2009) and 29% (2012). The mean total cost per woman treated in 2006 was €1111 (95% CI €808 to 1426), €436 (95% CI €307 to 590) in 2009 and €633 (95% CI €586 to 788) in 2012. We can therefore conclude that an EPAU results in higher quality and cost-effective care, and has a positive effect on early pregnancy care., (Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Intrauterine insemination (IUI), with or without ovarian stimulation, IVF and intracytoplasmatic sperm injection (ICSI) are frequently used treatments for couples with male subfertility. No consensus has been reached on specific cut-off values for semen parameters, at which IVF would be advocated over IUI and ICSI over IVF. The aim of this study was to evaluate the cost-effectiveness of interventions for male subfertility according to total motile sperm count (TMSC). A computer-simulated cohort of subfertile women aged 30 years with a partner was analysed with a pre-wash TMSC of 0 to 10 million. Three treatments were evaluated: IUI with and without controlled ovarian stimulation; IVF; and ICSI. Main outcome was expected live birth; secondary outcomes were cost per couple and the incremental cost-effectiveness ratio. The choice of IVF over IUI with ovarian stimulation and ICSI over IVF depends on the willingness to pay for an extra live birth. If only cost per live birth is considered for each treatment, above a pre-wash TMSC of 3 million, IUI is less costly than IVF and, below a pre-wash, TMSC of 3 million ICSI is less costly. Effectiveness needs to be confirmed in a large randomized controlled trial., (Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The selection of embryos based on morphology is still the core of daily laboratory practice in IVF/intracytoplasmic sperm injection. At present, the selection of embryos is primarily based on experience and local protocols. Since an evidence-based ranking strategy for embryos on day 3 is currently lacking, this work constructed a multivariable prediction model to rank embryos according to their implantation potential. A total of 6021 fresh embryo transfers between January 2004 and July 2009 were included, eight potential predictive factors were evaluated and a prediction model was developed using multivariable logistic regression. The model was externally validated with data from couples treated between August 2009 and September 2011 in the same clinic. Five factors were included in the final prediction model: early cleavage, number of blastomeres on days 2 and 3 and morphological score and presence of morula on day 3. With validation, the model showed moderate discriminative capacity (c-statistic 0.70) and calibrated well and was able to distinguish embryos with high ongoing implantation potential from embryos with moderate or low ongoing implantation potential. The model can be used by embryologists as an objective tool to rank embryos according to implantation potential, thereby aiding the selection of embryos for transfer., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

A previous randomized clinical trial compared immobilization for 15 min with immediate mobilization subsequent to intrauterine insemination (IUI) and showed higher ongoing pregnancy rates in couples immobilizing subsequent to IUI. The current study compared the long-term effectiveness of immobilization subsequent to IUI. All couples (n = 391) included in the trial were followed for 3 years after randomization and pregnancies and treatments were recorded. After the initial trial period, couples in both groups were offered treatment according to local protocol. The primary outcome was an ongoing pregnancy during the 3 years after the initial trial. In this time period, there were 143 ongoing pregnancies in the immobilization group (n = 199 couples) and 112 ongoing pregnancies in the immediate mobilization group (n = 192). The ongoing pregnancy rates were 72% and 58%, respectively (relative risk 1.2, 95% CI 1.1-1.4). The persistent significant difference in ongoing pregnancy rates underpins the importance of immobilization after IUI. There is no valid reason to withhold women from immobilizing for 15 min after IUI., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Concerns have been expressed about the rapid introduction of new fertility treatments into clinical practice. Patients' perspectives on new treatments and their introduction into clinical practice are unexplored. Two alternative treatments for testicular sperm extraction followed by intracytoplasmic sperm injection in men with nonobstructive azoospermia (NOA), the formation of artificial sperm and autotransplantation of in vitro proliferated spermatogonial stem cells, are in a preclinical phase of development. This study aimed to explore, prior to future clinical introduction, which treatment aspects are valued by NOA patients and would be taken into account in deciding to undergo these future treatment options. In-depth telephone interviews were conducted with 14 men with NOA. Interviews were transcribed, analysed with content analysis and data saturation was reached. Besides the obvious factors, success rates and safety, patients valued 'the intensity of the procedure', 'the treatments' resemblance to natural conception' and 'feeling cured'. Patients supported the development of these treatments and were eager to take part if such treatments would become available in the future. The patient's perspective on innovative treatments can (co)direct reproductive research. More research into the patients' perspectives on innovations and minimal thresholds to be met prior to their introduction into clinical practice is required., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

This study evaluated the cost-effectiveness of treatments for women with polycystic ovary syndrome (PCOS) who ovulate on clomiphene citrate but do not conceive after six cycles. A decision-analytic framework was developed for six scenarios: (1) three cycles of IVF; (2) continuation of clomiphene citrate for six cycles, followed by three cycles of IVF in case of no birth; (3) six cycles of gonadotrophins and three cycles of IVF; (4) 12 cycles of gonadotrophins and three cycles of IVF; (5) continuation of clomiphene citrate for six cycles, six cycles of gonadotrophins and three cycles of IVF; (6) continuation of clomiphene citrate for six cycles, 12 cycles of gonadotrophins and three cycles of IVF. Two-year cumulative birth rates were 58%, 74%, 89%, 97%, 93% and 98% and costs per couple were € 9518, € 7530, € 9711, € 9764, € 7651 and € 7684 for scenarios 1-6, respectively. Scenario 2 was the lowest cost option. The extra cost for at least one live birth in scenario 5 was € 629 and in scenario 6 € 630. In these subjects, continuation of treatment for six cycles of clomiphene citrate, 6 or 12 cycles of gonadotrophins and IVF is potentially cost-effective. These results should be confirmed in a randomized clinical trial., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The scope of female fertility preservation through cryopreservation of oocytes or ovarian cortex has widened from mainly oncological indications to a variety of fertility-threatening conditions. So far, no specific universally accepted denomination name has been given to cryopreservation of oocytes or ovarian cortex for the prevention of age-related fertility decline. We argue that the commonly used phrases 'social' and 'nonmedical freezing' to denote the indication for cryopreservation are not entirely correct. We suggest 'AGE banking', as this has not only the advantage of being catchy but also depicts the exact indication for the strategy, anticipated gamete exhaustion., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Tubal ectopic pregnancy can be surgically treated by salpingectomy, in which the affected Fallopian tube is removed, or salpingotomy, in which the tube is preserved. Despite potentially increased risks of persistent trophoblast and repeat ectopic pregnancy, salpingotomy is often preferred over salpingectomy because the preservation of both tubes is assumed to offer favourable fertility prospects, although little evidence exists to support this assumption. We aimed to assess whether salpingotomy would improve rates of ongoing pregnancy by natural conception compared with salpingectomy., Methods: In this open-label, multicentre, international, randomised controlled trial, women aged 18 years and older with a laparoscopically confirmed tubal pregnancy and a healthy contralateral tube were randomly assigned via a central internet-based randomisation program to receive salpingotomy or salpingectomy. The primary outcome was ongoing pregnancy by natural conception. Differences in cumulative ongoing pregnancy rates were expressed as a fecundity rate ratio with 95% CI, calculated by Cox proportional-hazards analysis with a time horizon of 36 months. Secondary outcomes were persistent trophoblast and repeat ectopic pregnancy (expressed as relative risks [RRs] with 95% CIs) and ongoing pregnancy after ovulation induction, intrauterine insemination, or IVF. The researchers who collected data for fertility outcomes were masked to the assigned intervention, but patients and the investigators who analysed the data were not. All endpoints were analysed by intention to treat. We also did a (non-prespecified) meta-analysis that included the findings from the present trial. This trial is registered, number ISRCTN37002267., Findings: 446 women were randomly assigned between Sept 24, 2004, and Nov 29, 2011, with 215 allocated to salpingotomy and 231 to salpingectomy. Follow-up was discontinued on Feb 1, 2013. The cumulative ongoing pregnancy rate was 60·7% after salpingotomy and 56·2% after salpingectomy (fecundity rate ratio 1·06, 95% CI 0·81-1·38; log-rank p=0·678). Persistent trophoblast occurred more frequently in the salpingotomy group than in the salpingectomy group (14 [7%] vs 1 [<1%]; RR 15·0, 2·0-113·4). Repeat ectopic pregnancy occurred in 18 women (8%) in the salpingotomy group and 12 (5%) women in the salpingectomy group (RR 1·6, 0·8-3·3). The number of ongoing pregnancies after ovulation induction, intrauterine insemination, or IVF did not differ significantly between the groups. 43 (20%) women in the salpingotomy group were converted to salpingectomy during the initial surgery because of persistent tubal bleeding. Our meta-analysis, which included our own results and those of one other study, substantiated the results of the trial., Interpretation: In women with a tubal pregnancy and a healthy contralateral tube, salpingotomy does not significantly improve fertility prospects compared with salpingectomy., Funding: Netherlands Organisation for Health Research and Development (ZonMW), Region Västra Götaland Health & Medical Care Committee., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Couples with unexplained subfertility are often treated with intrauterine insemination (IUI) with ovarian stimulation, which carries the risk of multiple pregnancies. An explorative randomized controlled trial was performed comparing one cycle of IVF with elective single-embryo transfer (eSET) versus three cycles of IUI-ovarian stimulation in couples with unexplained subfertility and a poor prognosis for natural conception, to assess the economic burden of the treatment modalities. The main outcome measures were ongoing pregnancy rates and costs. This study randomly assigned 58 couples to IVF-eSET and 58 couples to IUI-ovarian stimulation. The ongoing pregnancy rates were 24% in with IVF-eSET versus 21% with IUI-ovarian stimulation, with two and three multiple pregnancies, respectively. The mean cost per included couple was significantly different: €2781 with IVF-eSET and €1876 with IUI-ovarian stimulation (P<0.01). The additional costs per ongoing pregnancy were €2456 for IVF-eSET. In couples with unexplained subfertility, one cycle of IVF-eSET cost an additional €900 per couple compared with three cycles of IUI-ovarian stimulation, for no increase in ongoing pregnancy rates or decrease in multiple pregnancies. When IVF-eSET results in higher ongoing pregnancy rates, IVF would be the preferred treatment. Couples that have been trying to conceive unsuccessfully are often treated with intrauterine insemination (IUI) and medication to improve egg production (ovarian stimulation). This treatment carries the risk of multiple pregnancies like twins. We performed an explorative study among those couples that had a poor prognosis for natural conception. One cycle of IVF with transfer of one selected embryo (elective single-embryo transfer, eSET) was compared with three cycles of IUI-ovarian stimulation. The aim of this study was to assess the economic burden of both treatments. The Main outcome measures were number of good pregnancies above 12weeks and costs. We randomly assigned 58 couples to IVF-eSET and 58 couples to IUI-ovarian stimulation. The ongoing pregnancy rates were comparable: 24% with IVF-eSET versus 21% with IUI-ovarian stimulation. There were two multiple pregnancies with IVF-eSET and three multiple pregnancies with IUI-ovarian stimulation. The mean cost per included couple was significantly different, €2781 with IVF-eSET and €1876 with IUI-ovarian stimulation. The additional costs per ongoing pregnancy were €2456 for IVF-eSET. In couples with unexplained subfertility, one cycle of IVF-eSET costed an additional €900 per couple compared to three cycles of IUI-ovarian stimulation, for no increase in ongoing pregnancy rates or decrease in multiple pregnancies. We conclude that IUI-ovarian stimulation is the preferred treatment to start with. When IVF-eSET results in a higher ongoing pregnancy rate (>38%), IVF would be the preferred treatment., (Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

This study evaluated the lifetime future net tax revenues from individuals conceived after IVF relative to those naturally conceived. A model based on the method of generational accounting was developed to evaluate investments in IVF. Calculations were based on average investments paid and received from the government by an individual. All costs were discounted to their net present values and adjusted for survival. The lifetime net present value of IVF-conceived individuals was -€81,374 (the minus sign reflecting negative net present value). The lifetime net present value of IVF-conceived men and women were -€47,091 and -€123,177, respectively. The lifetime net present value of naturally conceived individuals was -€70,392; respective amounts for men and women were -€36,109 and -€112,195. The model was most sensitive to changes in the growth of healthcare costs, economic growth and the discount rate. Therefore, it is concluded that, similarly to naturally conceived individuals in the Netherlands, IVF-conceived individuals have negative discounted net tax revenue at the end of life. The analytic framework described here undervalues the incremental value of an additional birth because it only considers the fiscal consequences of life and does not take into consideration broader macroeconomic benefits. This study evaluated the lifetime future net tax revenues from individuals conceived after IVF relative those naturally conceived. A model based on the method of generational accounting to evaluate investments in IVF was used. Calculations were based on average investments paid and received from the government by an individual. The lifetime net present value of IVF-conceived individuals was -€81,374 (the minus sign reflecting negative net present value). The lifetime net present value of IVF-conceived men and women were -€47,091 and -€123,177, respectively. The lifetime net present value of naturally conceived individuals was -€70,392; respective amounts for men and women were -€36,109 and -€112,195. The model was most sensitive for changes in the growth in healthcare costs, economic growth and the discount rate. Just as naturally conceived individuals in the Netherlands, IVF-conceived individuals have negative discounted net tax revenue at the end of life. The analytic framework described here undervalues the incremental value of an additional birth because it only considers the fiscal consequences of life and does not take into consideration broader macroeconomic benefits., (Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

A tailored embryo transfer policy based on the prognostic profile of the couple was prospectively evaluated. Single-embryo transfer (SET) was performed, followed by double-embryo transfer (DET) in frozen-thawed embryo transfer cycles in women with a good prognosis (<35 years, first cycle, ⩾1 top-quality embryo). DET was performed in both fresh and frozen cycles in women with an intermediate prognosis (<35 years, first cycle and no top-quality embryo available, or <35 years and ⩾1 failed cycles, or 35-38 years). Triple-embryo transfer (TET) in both fresh and frozen cycles was performed in women with a poor prognosis (⩾39 years). The cumulative ongoing pregnancy rate in the cycles of women with a good prognosis was 43% with a multiple pregnancy rate of 2%, in the cycles of women with an intermediate prognosis 27% and 23% and in the cycles of women with a poor prognosis 18% and 13%, respectively. These findings can be used to guide current practice: i.e. performing SET in women with a good prognosis and TET in women with a poor prognosis. The embryo transfer strategy in women with an intermediate prognosis requires further improvement, possibly by refining the prognosis according to the ovarian response after ovarian stimulation., (Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Limited information exists about the real impact of the etiology of shock on early and late outcome after emergency surgery in acute native mitral valve endocarditis (ANMVE). This multicenter study analyzed the impact of the etiology of shock on early and late outcome in patients with ANMVE., Methods: Data were collected in eight institutions. Three hundred-seventy-nine ANMVE patients undergoing surgery on an emergency basis between May 1991 and December 2009 were eligible for the study. According to current criteria used for the differential diagnosis of shock, patients were retrospectively assigned to one of three groups: group 1, no shock (n=154), group 2, cardiogenic shock (CS [n=118]), and group 3, septic shock (SS [n=107]). Median follow-up was 69.8 months., Results: Early mortality was significantly higher in patients with SS (p<0.001). At multivariable logistic regression analysis, compared with patients with CS, patients with SS had more than 3.8 times higher risk of death. That rose to more than 4 times versus patients without shock. In addition, patients with SS had 4.2 times and 4.3 times higher risk of complications compared with patients with CS and without shock, respectively. Sepsis was also an independent predictor of prolonged artificial ventilation (p=0.04) and stroke (p=0.003) whereas CS was associated with a higher postoperative occurrence of low output syndrome and myocardial infarction (p<0.001). No difference was detected between groups in 18-year survival, freedom from endocarditis, and freedom from reoperation., Conclusions: Our study suggests that emergency surgery for ANMVE in patients with CS achieved satisfactory early and late results. In contrast, the presence of SS was linked to dismal early prognosis. Our findings need to be confirmed by further larger studies., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Couples with recurrent miscarriage (RM) and men with poor semen quality may undergo genetic testing as part of the diagnostic work-up. This study explored their knowledge and perception of genetic testing, evaluated psychological wellbeing and identified associated variables. A prospective questionnaire study was conducted in seven clinical genetics centres and referring gynaecological departments in couples with RM or poor semen quality. Questionnaires were completed before disclosure of genetic test results. Main outcome measures were knowledge, perceived risk, anxiety and depression. Of 439 participants, 256 were not aware genetic testing was part of the diagnostic work-up. One-third (36% RM, 33% poor semen quality) indicated they had not received information about the genetic test from their doctor. Perceived risk of receiving an abnormal genetic test result was higher than objective risk. Anxiety was highly correlated with perceived risk. Women with RM were more anxious than women in the poor semen quality group or men (P<0.01). These couples undergoing genetic testing have a suboptimal understanding of the nature of testing, overestimate the risks of receiving an abnormal result and some show high levels of anxiety. The results of this study can be used to improve patient counselling before genetic testing., (Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Prediction models for IVF can be used to identify couples that will benefit from IVF treatment. Currently there is only one prediction model with a good predictive performance that can be used for predicting pregnancy chances after IVF. That model was developed almost 15 years ago and since IVF has progressed substantially during the last two decades it is questionable whether the model is still valid in current clinical practice. The objective of this study was to validate the prediction model of Templeton for calculating pregnancy chances after IVF. The performance of the prediction model was assessed in terms of discrimination, i.e. the area under the receiver operation characteristic (ROC) curve and calibration. Likely causes for miscalibration were evaluated by refitting the Templeton model to the study data. The area under the ROC curve for the Templeton model was 0.61. Calibration showed a significant and systematic underestimation of success in IVF. Although the Templeton model can distinguish somewhat between women with a high and low success rate in IVF, it systematically underestimates pregnancy chances and has therefore no real value for current IVF practice., (Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

There is an ongoing debate whether tubal ectopic pregnancy should be treated by salpingotomy or salpingectomy. It is unknown which treatment women prefer in view of the potentially better fertility outcome but disadvantages of salpingotomy. This study investigated women surgically treated for tubal ectopic pregnancy and subfertile women desiring pregnancy and their preferences for salpingotomy relative to salpingectomy by means of a web-based discrete choice experiment consisting of 16 choice sets. Scenarios representing salpingotomy differed in three attributes: intrauterine pregnancy (IUP) chance, risk of persistent trophoblast and risk of repeat ectopic pregnancy. An 'opt out' alternative, representing salpingectomy, was similar for every choice set. A multinomial logistic regression model was used to analyse relative importance of the attributes. This study showed that the negative effect of repeat ectopic pregnancy was 1.6 times stronger on the preference of women compared with the positive effect of the spontaneous IUP rate. For all women, the risk of persistent trophoblast was acceptable if compensated by a small rise in the spontaneous IUP rate. The conclusion was that women preferred avoiding a repeat ectopic pregnancy to a higher probability of a spontaneous IUP in the surgical treatment of tubal ectopic pregnancy. An ectopic pregnancy occurs when a fertilized egg gets stuck inside the Fallopian tube where it starts growing instead of passing on to the uterus. This may lead to serious problems, such as internal bleeding and pain. Therefore, in the majority of women, it is necessary to remove the ectopic pregnancy by means of an operation. Two types of surgery are being used in removing the ectopic pregnancy. A conservative approach, salpingotomy, preserves the tube but bears the risk of incomplete removal of the pregnancy tissue (persistent trophoblast), which then needs additional treatment, and of a repeat ectopic pregnancy in the same tube in the future. A radical approach, salpingectomy, bears no risk of persistent trophoblast and limits the risk of repeat tubal pregnancy, but leaves only one tube for reproductive capacity. It is unknown which type of operation is better, especially for future fertility. We investigated women's preferences between these two treatments for ectopic pregnancy, i.e. does a better fertility prognosis outweigh the potential disadvantages of persistent trophoblast and an increased risk for ectopic pregnancy in the future? The study results show in the surgical treatment of tubal ectopic pregnancy that women preferred avoiding a repeat ectopic pregnancy to gaining a higher chance of a spontaneous intrauterine pregnancy. The risk of additional treatment in the case of persistent trophoblast after salpingotomy was acceptable if compensated by a small rise in intrauterine pregnancy rate., (Copyright © 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Tubal pathology is a common cause of subfertility. Identifying risk factors for tubal pathology in the medical history is important to distinguish between those couples who benefit from early tubal patency tests and those in whom presence of tubal pathology is less likely and delaying tubal tests is justified. This study evaluated whether a medical history of induced abortion is associated with an increased risk of tubal disease among subfertile couples. The reproductive history was determined for each couple. Tubal disease was diagnosed by hysterosalpingography and/or diagnostic laparoscopy. The association between reproductive history and the presence of tubal disease was assessed by calculating odds ratios (OR) and 95% confidence intervals (CI). Data from 6149 couples were available for analysis. The OR for tubal pathology after a previous induced abortion was 1.6 (95% CI 1.3 to 1.9), after a previous ectopic pregnancy, 8.4 (95% CI 6.3 to 12), after a previous spontaneous miscarriage, 1.1 (95% CI 0.87 to 1.3), and after a previous live birth, 1.0 (95% CI 0.88 to 1.2). A history of induced abortion is associated with an increased risk of tubal pathology in subfertile couples. As a consequence, in subfertile women with a history of induced abortion, tubal patency tests should be considered early in the diagnostic work-up.

Patients' preferences for intrauterine insemination (IUI) relative to IVF were assessed using trade-off interviews, and the number of IUI cycles they would undergo before changing to IVF. A total of 73 couples undergoing IUI with a total of 111 interviews were included. Scenarios were offered where pregnancy chance after IUI was varied against a fixed pregnancy rate after IVF. The impact of multiple pregnancy risk on the couple's preference was also investigated. Interviews were held before starting IUI, after three or four IUI cycles and after six IUI cycles. With decreasing probability of ongoing pregnancy after IUI, an increasing number of couples switched their preference from IUI to IVF. This switch occurred after six cycles at a significantly higher (P = 0.01) mean cumulative pregnancy rate (53%) compared with other groups (31%). With increasing risk of multiple pregnancy, preference for IUI declined only slightly, with mean risks of 73, 78 and 83% of a multiple pregnancy for the three groups respectively. In conclusion, at baseline and after three cycles of IUI the majority of couples undergoing IUI preferred continuation of IUI over IVF. A clear shift in preference towards IVF occurred after six cycles. Risk of multiple pregnancy did not affect preference for IUI with ovarian stimulation.

The aim of this retrospective study was to assess the results of intrauterine insemination (IUI) in The Netherlands, using data from 2003 taken from hospital annual reports and reports from individual gynaecologists. By extrapolation, the total number of IUI cycles performed that year nationwide, and the related outcomes, was estimated. IUI was performed in 91 of the country's 101 hospitals. Of these, 58 (64%) registered their IUI results and performed 19,846 IUI cycles. The mean pregnancy rate per cycle was 9.0% and the ongoing pregnancy rate per cycle was 7.3%. Multiple pregnancies occurred in 9.5% of the ongoing pregnancies. Extrapolation of the data suggested that approximately 28,500 IUI cycles were performed, of which approximately 2000 resulted in an ongoing pregnancy. The number of multiple pregnancies following IUI was estimated to be 180 (9.0%). According to the national IVF registry, 9761 IVF cycles were started in 2003, resulting in 2,028 ongoing pregnancies (20.8% per cycle) and 439 twin pregnancies (21.6% per ongoing pregnancy). In conclusion, the pregnancy rate per IUI cycle in The Netherlands (9.0%) was comparable with that reported in the international literature (8.7%). The contribution made by IUI to the number of multiple pregnancies in The Netherlands was much smaller than the contribution made by IVF.

In the last century, there was a heated debate on whether fetal growth retardation is caused by a small placenta or whether a placenta is small because the baby is small. One of the active participants in this debate was Kloosterman who studied 80,000 birth weights, and 30,000 placental weights, in relation to gestational age at birth, fetal sex, maternal parity, and perinatal mortality. He found that pregnancies related to heavier placentas last longer. He also found that, from about 32 weeks of gestation onwards, children from primiparous women as compared to those from multiparous women, like twin children as compared to singleton children, are relatively growth retarded, most likely related to prior relatively poor placental growth. He concluded that poor fetal growth is not the cause, but the result of poor placental growth. The clinical implication of all these is that future early detection of poor placental growth may prospect poor fetal growth, and may even allow for early interventions to improve fetal outcome.

Background: Intrauterine insemination with controlled ovarian hyperstimulation is commonly used as first-line treatment for couples with unexplained subfertility. Since such treatment increases the risk of multiple pregnancy, a couple's chances of achieving an ongoing pregnancy without it should be considered to identify those most likely to benefit from treatment. We aimed to assess the incremental effectiveness of intrauterine insemination with controlled ovarian hyperstimulation compared with expectant management in couples with unexplained subfertility and an intermediate prognosis of a spontaneous ongoing pregnancy., Methods: 253 couples with unexplained subfertility and a 30-40% probability of a spontaneous ongoing pregnancy within 12 months were randomly assigned either intrauterine insemination with controlled ovarian hyperstimulation for 6 months or expectant management for 6 months. The primary endpoint of this hospital-based study was ongoing pregnancy within 6 months. Analysis was by intention to treat. This trial is registered with the Dutch Trial Register and as an International Standard Randomised Clinical Trial, number ISRCTN72675518., Findings: Of the 253 couples enrolled, 127 were assigned intrauterine insemination with controlled ovarian hyperstimulation and 126 expectant management. In the intervention group, 42 (33%) women conceived and 29 (23%) pregnancies were ongoing. In the expectant management group, 40 (32%) women conceived and 34 (27%) pregnancies were ongoing (relative risk 0.85, 95% CI 0.63-1.1). There was one twin pregnancy in each study group, and one woman in the intervention group conceived triplets., Interpretation: A large beneficial effect of intrauterine insemination with controlled ovarian hyperstimulation in couples with unexplained subfertility and an intermediate prognosis can be excluded. Expectant management for 6 months is therefore justified in these couples.

Sixteen vignettes of subfertile couples were constructed by varying fertility history, post-coital test, sperm motility, FSH concentration and Chlamydia antibody titre (CAT). Thirty-five gynaecologists estimated probabilities of treatment-independent pregnancy, intrauterine insemination (IUI) and IVF. Thereafter, they chose IUI, IVF or no treatment. The relative contribution of each factor to probability estimates and to subsequent treatment decisions was calculated. Duration of subfertility and maternal age were the most important contributors for gynaecologists' estimates of treatment-independent pregnancy [relative contribution (RC) 41, 26%]. Maternal age and FSH concentration were the most important contributors in the estimates for IUI (RC: 51, 25%) and for IVF (RC: 64, 31%). The decision to start IVF was mainly determined by maternal age, duration of subfertility, FSH concentration and CAT. The relative contribution of maternal age and duration of subfertility was in concordance with existing prediction models, whereas previous pregnancy and FSH concentration were under- and overestimated respectively. In conclusion, maternal age, duration of subfertility and FSH concentration are the main factors in clinical decision-making in subfertility. Gynaecologists overestimate the importance of FSH concentration, but underestimate that of a previous pregnancy, as compared with their importance reported in prediction models and guidelines.

There is at this time no indication as to which semen parameters from the fertility work-up discriminate between couples with male subfertility who will and will not benefit from intrauterine insemination (IUI). This study evaluated the predictive capacity of semen parameters (both pre- and post-wash) and antisperm antibodies (ASA) obtained during the fertility workup on IUI outcome in couples with male subfertility in a retrospective cohort study. It included 290 couples, who underwent 722 IUI cycles. The overall ongoing pregnancy rate was 9% per cycle. Model I, with female age, duration of subfertility, secondary subfertility, the presence of anovulation, cervical hostility and cycle number had an area under the curve (AUC) of 0.59. Adding the presence of ASA to this model improved the AUC to 0.65 (model II). Further addition of the post-wash total motile count (TMC) to the model with ASA (model III) improved the AUC to 0.67. Using the models to exclude couples from IUI due to low expected pregnancy rates would increase the pregnancy rate to 11% per cycle with model I, and to 14% per cycle for model II and for model III. In conclusion, in the selection of patients with male subfertility for IUI, the use of prediction models including ASA can increase the efficiency of IUI.

Objective: Clinical data have suggested the occurrence of temporary short-term deterioration of the heart following cardiomyoplasty. The purpose of this study was to monitor the short-term hemodynamic effects of cardiomyoplasty in a goat model of a dilated left ventricle, using conductance catheters (ie, pressure-volume loops) and cardiac output measurements., Methods: Eight female goats underwent acute cardiomyoplasty 8 to 12 weeks after left ventricular (LV) dilatation was induced by a carotid jugular arteriovenous shunt. The cardiomyoplasty procedure was monitored using a Swan-Ganz catheter for cardiac output measurements and a 12-electrode (dual-field) conductance catheter to LV pressure-volume loops., Results: After wrapping the heart with the latissimus dorsi muscle, there was a significant reduction in both cardiac output and LV end-diastolic volume (LVEDV) at 10 min. Partial recovery was observed 45 min later., Conclusion: A decrease in both cardiac output and LVEDV was observed following myocardial wrapping. This may explain some of the perioperative and postoperative morbidity and mortality observed following cardiomyoplasty.

Background: Three-dimensional electromechanical mapping has previously been shown to be a clinically important tool for cardiac imaging and intervention. We hypothesized that this technology may be beneficial as an intraoperative modality for assessing cardiac hemodynamics and viability during cardiac surgery. We report here the use of this technology as an imaging modality for intraoperative cardiac surgery., Methods: The tip of a locatable catheter connected to an endocardial mapping and navigating system is accurately localized while simultaneously recording local electrical and mechanical functions. Thus the three-dimensional geometry of the beating cardiac chamber is reconstructed in real time. The system was tested on 6 goats that underwent acute dynamic cardiomyoplasty and on 5 dogs that underwent left anterior descending (LAD) coronary artery ligation., Results: The electromechanical mapping system provided an accurate three-dimensional reconstruction of the beating left ventricle during cardiomyoplasty. After the wrapping procedure, significant end-diastolic area reduction was noted in the base and mid parts of the heart (948 +/- 194 mm2 vs 1245 +/- 33 mm2, p = 0.021; and 779 +/- 200 mm2 vs 1011 +/- 80 mm2, p = 0.016). The area of the cross-section of the apex did not change during the operation. Acute infarcted tissue was characterized 3 days after LAD ligation by concomitant deterioration in both electrical and mechanical function., Conclusions: By providing both a clear view of the anatomical changes that occur during cardiac surgery, and an accurate assessment of tissue viability, electroanatomic mapping may serve as an important adjunct tool for imaging and analysis of the heart during cardiac surgery

Background: Aortomyoplasty is a procedure aimed to improve cardiac output in patients suffering from heart failure. Stimulation of the latissimus dorsi muscle around the aorta produces hemodynamic effects similar to those of the intraaortic balloon pump. These may be maintained without the accompanying complications or the need for anticoagulation. The objective of this study was to test the acute effects of aortomyoplasty on coronary artery blood flow., Methods: Eight mongrel dogs (18 to 30 kg) underwent acute descending aortomyoplasty. Several stimulation protocols were applied after wrapping of the latissimus dorsi muscle around the aorta in different surgical configurations. The left anterior descending coronary blood flow was measured using a transonic Doppler flow probe. Left ventricular and aortic pressures, proximal and distal to the aortomyoplasty site, were monitored continuously., Results: Significant aortic diastolic pressure augmentation was expressed both as an increase in peak values, from 110 +/- 24 mm Hg to 120 +/- 24 mm Hg (p < 0.001) and as an increase in the diastolic integral, from 64 +/- 23 mm Hg x s to 84 +/- 37 mm Hg x s (p < 0.001). Concomitantly, peak left anterior descending coronary blood flow increased from 26 +/- 10 mL/min to 32 +/- 12 mL/min (p < 0.001). This was associated with an increase in the diastolic flow integral from 11 +/- 4 mL to 14 +/- 6 mL (p < 0.001)., Conclusions: Descending aortomyoplasty induces significant augmentation of coronary blood flow. Optimal timing of muscle stimulation is important in achieving the best assist. This procedure may prove beneficial for end-stage ischemic patients.

Objective: This study was undertaken to compare from a societal perspective the costs of systemic methotrexate administration with those of laparoscopic salpingostomy for the treatment of patients with tubal pregnancy., Study Design: An economic evaluation was set up in tandem with a multicenter randomized clinical trial that compared systemic methotrexate administration and laparoscopic salpingostomy for the treatment of 100 hemodynamically stable patients with laparoscopically confirmed unruptured tubal pregnancy. Data on resources used for treatment and lost production time were prospectively collected and costs of both treatments were calculated by multiplying actual expenses for resource units at a single center and resource unit use measured in all centers. Costs were originally calculated in Dutch guilders and converted to US dollars at a rate of 1.67 guilders/$1., Results: Because clinical outcomes of the trial were equivalent for the 2 strategies a cost-minimization analysis was done. Mean total costs per patient were $5721 for systemic methotrexate administration and $4066 for laparoscopic salpingostomy, with a mean difference of $1655 (95% confidence interval, $906-$2414). Costs of systemic methotrexate administration were similar to those of salpingostomy for patients in whom the initial serum human chorionic gonadotropin concentration was <1500 IU/L, a cutoff value that had not been previously hypothesized. In a scenario without a confirmatory laparoscopy, in which transvaginal ultrasonography and serial repeated serum human chorionic gonadotropin measurements were assumed to be as accurate as laparoscopy, systemic methotrexate therapy would have reduced total cost by $1500 for a patient with an initial serum human chorionic gonadotropin concentration of <1500 IU/L. In such a scenario total costs would have been similar for a patient with an initial serum human chorionic gonadotropin concentration in the range of 1500 to 3000 IU/L, whereas systemic methotrexate administration would be more costly for a patient with an initial serum human chorionic gonadotropin concentration of >3000 IU/L., Conclusions: Although systemic methotrexate administration is safe and effective for the treatment of tubal pregnancy, it does not necessarily reduce costs. Systemic methotrexate therapy could reduce costs if administered to patients with low initial serum human chorionic gonadotropin concentrations without confirmatory laparoscopy.

Background: Beating heart coronary artery bypass graft surgery of the left anterior descending, diagonal, and right coronary artery can be performed safely with the Octopus Stabilization System. However, tilting of the heart, which is necessary to reach the obtuse marginal and distal right coronary arteries, causes hemodynamic instability. This study was performed to investigate the possible role of the Enabler right ventricular circulatory support system in counteracting this instability., Methods: In 8 sheep, the Enabler cannula was introduced via the jugular vein and positioned with the inlet valve in the right atrium and outlet valve in the pulmonary artery. The Octopus was used to expose the inferior wall and the posterior wall of the left ventricle. The hemodynamic effects of this tilting with and without Enabler right ventricular support were recorded, including Pressure Volume (PV) loops measured by conductance catheters in both ventricles., Results: Tilting caused a reduction in stroke volume (inferior 31%, posterior 17%) and Enabler activation increased stroke volume (inferior 13%, posterior 31%)., Conclusions: Tilting the heart has severe hemodynamic consequences that can be partially counteracted by the use of the Enabler for right ventricle support.

Background: Laparoscopic salpingostomy is a well-established treatment for patients with tubal pregnancy who desire to retain fertility. Another approach that preserves the fallopian tube is medical treatment. We compared systemic methotrexate and laparoscopic salpingostomy in the treatment of tubal pregnancy. Outcome measures were treatment success, tubal preservation, and homolateral tubal patency., Methods: Between January, 1994, and September, 1996, haemodynamically stable patients with laparoscopically confirmed unruptured tubal pregnancy and no signs of active bleeding were randomly assigned systemic methotrexate (four 1.0 mg/kg doses of intramuscular methotrexate alternated with 0.1 mg/kg oral folinic acid) or laparoscopic salpingostomy. Treatment success was defined as complete elimination of the tubal pregnancy (serum human chorionic gonadotropin < 2 IU/L) and preservation of the tube. Homolateral tubal patency was assessed by hysterosalpingography. Analysis was by intention to treat., Findings: 100 patients were included in the trial. Of 51 patients allocated systemic methotrexate, 42 (82%) were successfully treated with one course; two (4%) patients needed a second course for persistent trophoblast. Surgical intervention was needed in seven (14%) patients; salpingectomy was necessary in five of these patients for tubal rupture. Of the 49 patients allocated laparoscopic salpingostomy, 35 (72%) were successfully treated by laparoscopic salpingostomy alone; salpingectomy was needed in four (8%) patients, and ten (20%) needed methotrexate for persistent trophoblast. The tube was preserved in 46 (90%) patients in the methotrexate group versus 45 (92%) in the salpingostomy group (rate ratio 0.98 [95% CI 0.87-1.1]). Homolateral tubal patency could be assessed in 81 patients: the tube was patent in 23 (55%) of 42 patients in the methotrexate group and in 23 (59%) of 39 patients in the salpingostomy group (rate ratio 0.93 [0.64-1.4])., Interpretation: In haemodynamically stable patients with unruptured tubal pregnancy, systemic methotrexate and laparoscopic salpingostomy were successful in treating the majority of cases. We found no significant difference between the treatments in the homolateral patency rate. Subsequent fertility outcome has to be awaited to show which treatment yields better fertility prospects.