RESUMEN
STUDY QUESTION: Is endometrial thickness (EMT) a biomarker to select between women who should switch to gonadotropins and those who could continue clomiphene citrate (CC) after six failed ovulatory cycles? SUMMARY ANSWER: Using a cut-off of 7 mm for EMT, we can distinguish between women who are better off switching to gonadotropins and those who could continue CC after six earlier failed ovulatory CC cycles. WHAT IS ALREADY KNOWN: For women with normogonadotropic anovulation, CC has been a long-standing first-line treatment in conjunction with intercourse or intrauterine insemination (IUI). We recently showed that a switch to gonadotropins increases the chance of live birth by 11% in these women over continued treatment with CC after six failed ovulatory cycles, at a cost of 15 258 per additional live birth. It is unclear whether EMT can be used to identify women who can continue on CC with similar live birth rates without the extra costs of gonadotropins. STUDY DESIGN, SIZE, DURATION: Between 8 December 2008 and 16 December 2015, 666 women with CC failure were randomly assigned to receive an additional six cycles with a change to gonadotropins (n = 331) or an additional six cycles continuing with CC (n = 335), both in conjunction with intercourse or IUI. The primary outcome was conception leading to live birth within 8 months after randomisation. EMT was measured mid-cycle before randomisation during their sixth ovulatory CC cycle. The EMT was available in 380 women, of whom 190 were allocated to gonadotropins and 190 were allocated to CC. PARTICIPANTS/MATERIALS, SETTING, METHODS: EMT was determined in the sixth CC cycle prior to randomisation. We tested for interaction of EMT with the treatment effect using logistic regression. We performed a spline analysis to evaluate the association of EMT with chance to pregnancy leading to a live birth in the next cycles and to determine the best cut-off point. On the basis of the resulting cut-off point, we calculated the relative risk and 95% CI of live birth for gonadotropins versus CC at EMT values below and above this cut-off point. Finally, we calculated incremental cost-effectiveness ratios (ICER). MAIN RESULTS AND THE ROLE OF CHANCE: Mid-cycle EMT in the sixth cycle interacted with treatment effect (P < 0.01). Spline analyses showed a cut-off point of 7 mm. There were 162 women (45%) who had an EMT ≤ 7 mm in the sixth ovulatory cycle and 218 women (55%) who had an EMT > 7 mm. Among the women with EMT ≤ 7 mm, gonadotropins resulted in a live birth in 44 of 79 women (56%), while CC resulted in a live birth in 28 of 83 women (34%) (RR 1.57, 95% CI 1.13-2.19). Per additional live birth with gonadotropins, the ICER was 9709 (95% CI: 5117 to 25 302). Among the women with EMT > 7 mm, gonadotropins resulted in a live birth in 53 of 111 women (48%) while CC resulted in a live birth in 52 of 107 women (49%) (RR 0.98, 95% CI 0.75-1.29). LIMITATIONS, REASONS FOR CAUTION: This was a post hoc analysis of a randomised controlled trial (RCT) and therefore mid-cycle EMT measurements before randomisation during their sixth ovulatory CC cycle were not available for all included women. WIDER IMPLICATIONS OF THE FINDINGS: In women with six failed ovulatory cycles on CC and an EMT ≤ 7 mm in the sixth cycle, we advise switching to gonadotropins, since it improves live birth rate over continuing treatment with CC at an extra cost of 9709 to achieve one additional live birth. If the EMT > 7 mm, we advise to continue treatment with CC, since live birth rates are similar to those with gonadotropins, without the extra costs. STUDY FUNDING/COMPETING INTEREST(S): The original MOVIN trial received funding from the Dutch Organization for Health Research and Development (ZonMw number: 80-82310-97-12067). C.B.L.A. reports unrestricted grant support from Merck and Ferring. B.W.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for Merck, ObsEva, IGENOMIX and Guerbet. All other authors have nothing to declare. TRIAL REGISTRATION NUMBER: Netherlands Trial Register, number NTR1449.
Asunto(s)
Anovulación , Anovulación/tratamiento farmacológico , Tasa de Natalidad , Clomifeno/uso terapéutico , Endometrio , Femenino , Gonadotropinas , Humanos , Nacimiento Vivo , Países Bajos , Inducción de la Ovulación , Embarazo , Índice de EmbarazoRESUMEN
STUDY QUESTION: Are six cycles of ovulation induction with gonadotrophins more cost-effective than six cycles of ovulation induction with clomiphene citrate (CC) with or without IUI in normogonadotropic anovulatory women not pregnant after six ovulatory cycles with CC? SUMMARY ANSWER: Both gonadotrophins and IUI are more expensive when compared with CC and intercourse, and gonadotrophins are more effective than CC. WHAT IS KNOWN ALREADY: In women with normogonadotropic anovulation who ovulate but do not conceive after six cycles with CC, medication is usually switched to gonadotrophins, with or without IUI. The cost-effectiveness of these changes in policy is unknown. STUDY DESIGN, SIZE, DURATION: We performed an economic evaluation of ovulation induction with gonadotrophins compared with CC with or without IUI in a two-by-two factorial multicentre randomized controlled trial in normogonadotropic anovulatory women not pregnant after six ovulatory cycles with CC. Between December 2008 and December 2015 women were allocated to six cycles with gonadotrophins plus IUI, six cycles with gonadotrophins plus intercourse, six cycles with CC plus IUI or six cycles with CC plus intercourse. The primary outcome was conception leading to a live birth achieved within 8 months of randomization. PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed a cost-effectiveness analysis on direct medical costs. We calculated the direct medical costs of ovulation induction with gonadotrophins versus CC and of IUI versus intercourse in six subsequent cycles. We included costs of medication, cycle monitoring, interventions, and pregnancy leading to live birth. Resource use was collected from the case report forms and unit costs were derived from various sources. We calculated incremental cost-effectiveness ratios (ICER) for gonadotrophins compared to CC and for IUI compared to intercourse. We used non-parametric bootstrap resampling to investigate the effect of uncertainty in our estimates. The analysis was performed according to the intention-to-treat principle. MAIN RESULTS AND THE ROLE OF CHANCE: We allocated 666 women in total to gonadotrophins and IUI (n = 166), gonadotrophins and intercourse (n = 165), CC and IUI (n = 163), or CC and intercourse (n = 172). Mean direct medical costs per woman receiving gonadotrophins or CC were 4495 versus 3006 (cost difference of 1475 (95% CI: 1457-1493)). Live birth rates were 52% in women allocated to gonadotrophins and 41% in those allocated to CC (relative risk (RR) 1.24:95% CI: 1.05-1.46). The ICER was 15 258 (95% CI: 8721 to 63 654) per additional live birth with gonadotrophins. Mean direct medical costs per woman allocated to IUI or intercourse were 4497 versus 3005 (cost difference of 1510 (95% CI: 1492-1529)). Live birth rates were 49% in women allocated to IUI and 43% in those allocated to intercourse (RR = 1.14:95% CI: 0.97-1.35). The ICER was 24 361 (95% CI: -11 290 to 85 172) per additional live birth with IUI. LIMITATIONS, REASONS FOR CAUTION: We allowed participating hospitals to use their local protocols for ovulation induction and IUI, which may have led to variation in costs, but which increases generalizability. Indirect costs generated by transportation or productivity loss were not included. We did not evaluate letrozole, which is potentially more effective than CC. WIDER IMPLICATIONS OF THE FINDINGS: Gonadotrophins are more effective, but more expensive than CC, therefore, the use of gonadotrophins in women with normogonadotropic anovulation who have not conceived after six ovulatory CC cycles depends on society's willingness to pay for an additional child. In view of the uncertainty around the cost-effectiveness estimate of IUI, these data are not sufficient to make recommendations on the use of IUI in these women. In countries where ovulation induction regimens are reimbursed, policy makers and health care professionals may use our results in their guidelines. STUDY FUNDING/COMPETING INTEREST(S): This trial was funded by the Netherlands Organization for Health Research and Development (ZonMw number: 80-82310-97-12067). The Eudract number for this trial is 2008-006171-73. The Sponsor's Protocol Code Number is P08-40. CBLA reports unrestricted grant support from Merck and Ferring. BWM is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for Merck, ObsEva and Guerbet. TRIAL REGISTRATION NUMBER: NTR1449.
Asunto(s)
Anovulación/tratamiento farmacológico , Análisis Costo-Beneficio , Fármacos para la Fertilidad Femenina/administración & dosificación , Infertilidad Femenina/terapia , Inseminación Artificial/economía , Inducción de la Ovulación/métodos , Adulto , Anovulación/sangre , Anovulación/complicaciones , Tasa de Natalidad , Clomifeno/administración & dosificación , Clomifeno/economía , Femenino , Fármacos para la Fertilidad Femenina/economía , Gonadotropinas/administración & dosificación , Gonadotropinas/sangre , Gonadotropinas/economía , Costos de la Atención en Salud/estadística & datos numéricos , Humanos , Infertilidad Femenina/sangre , Infertilidad Femenina/etiología , Nacimiento Vivo , Masculino , Países Bajos , Inducción de la Ovulación/economía , Embarazo , Índice de Embarazo , Insuficiencia del TratamientoRESUMEN
STUDY QUESTION: Is pre-ovulatory endometrial thickness (EMT) in women with unexplained subfertility undergoing IUI with ovarian stimulation (OS) associated with pregnancy chances? SUMMARY ANSWER: We found no evidence for an association between EMT and pregnancy chances. WHAT IS KNOWN ALREADY: It has been suggested that OS with clomiphene citrate (CC) results in a lower EMT than with gonadotrophins or aromatase inhibitors, but the clinical consequences in terms of pregnancy are unclear. STUDY DESIGN, SIZE, DURATION: We performed a systematic review and meta-analysis of studies comparing CC, gonadotrophins or aromatase inhibitors in an IUI program reporting on EMT and pregnancy rates in women with unexplained subfertility. PARTICIPANTS/MATERIALS, SETTING, METHODS: We searched MEDLINE, EMBASE and the non-MEDLINE subset of PubMed from inception to 28th June 2016 and cross-checked references of relevant articles. Outcome measures were clinical pregnancy rate and mean pre-ovulatory EMT. We calculated mean differences (MD) with 95% CIs with a fixed effect model, and in case of heterogeneity with an I2 > 50% a random effect model. We performed a meta-regression analysis to determine if stimulating drugs interacted with the estimated effect of EMT. MAIN RESULTS AND THE ROLE OF CHANCE: Our search retrieved 1563 articles of which 23 were included, totaling 3846 women. There were 17 RCTs and 6 cohort studies. The average study quality was low and there was considerable to substantial statistical heterogeneity. Seven studies provided data on EMT in relation to pregnancy. There was no evidence of a difference in EMT between women who conceived and women that did not conceive (1525 women, MDrandom: 0.51 mm, 95% CI: -0.05 to 1.07). Women treated with CC had a significantly thinner EMT than women treated with gonadotrophins (two studies, MD: -0.33, 95% CI: -0.64 to -0.01). There was no evidence of a difference in EMT when comparing CC with letrozole (five studies, MDrandom: -0.84, 95% CI: -1.97 to 0.28). The combination of CC plus gonadotrophins resulted in a slightly thinner endometrium than letrozole (nine studies, MDrandom: -0.79, 95% CI: -1.37 to -0.20). Letrozole resulted in a thinner EMT than gonadotrophins (two studies, MDrandom: -1.31, 95% CI: -2.08 to -0.53). LIMITATIONS, REASONS FOR CAUTION: The overall quality of the included studies was low to moderate. We found considerable to substantial heterogeneity in the comparisons, hampering firm conclusions. WIDER IMPLICATIONS OF THE FINDINGS: We found no evidence for an association between EMT and pregnancy rates during IUI -OS. As a consequence, canceling IUI cycles because of a thin endometrial lining may negatively affect clinical care. Although we found some evidence for very small differences in EMT when comparing various drugs, we cannot make inferences on their effect on pregnancy chances since these differences may be coincidental. STUDY FUNDING/COMPETING INTEREST(S): None. REGISTRATION NUMBER: N/A.
Asunto(s)
Endometrio/diagnóstico por imagen , Inseminación Artificial/métodos , Inducción de la Ovulación/métodos , Femenino , Humanos , Nacimiento Vivo , Tamaño de los Órganos , Embarazo , Resultado del Embarazo , Índice de EmbarazoRESUMEN
Although the prevailing opinion is that emotional processes are influenced by sex hormones, the literature is still inconclusive. The aim of the current study was to examine the effects of gonadal suppression on brain activity during affective picture processing. Twenty-one female-to-male (FtM) transsexuals and 19 control women were recruited and underwent functional magnetic resonance imaging scanning while rating emotional pictures adapted from the International Affective Picture System. The gonadal hormone production of the FtMs was suppressed for 8 weeks, the control group did not receive any treatment before scanning. Under gonadal suppression, FtMs showed less brain activation in the superior temporal lobe compared with female controls during perception of positive affective pictures. Regression analysis showed that during processing of positive affective images, brain activity within the right superior temporal lobe was not correlated with levels of estradiol, luteinizing hormone, and follicle-stimulating hormone. In the absence of associations with hormonal levels, the difference in activation in the superior temporal lobe during positive emotional stimuli between FtMs and control women may be attributed to a priori differences between the 2 groups. Future studies should clarify if these differences are a result of atypical sexual differentiation of the brain in FtMs.
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Mapeo Encefálico , Encéfalo/fisiopatología , Emociones/fisiología , Hormonas Esteroides Gonadales/sangre , Transexualidad/patología , Adolescente , Adulto , Encéfalo/irrigación sanguínea , Estradiol , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Oxígeno/sangre , Estimulación Luminosa , Escalas de Valoración Psiquiátrica , Radioinmunoensayo , Tiempo de Reacción/fisiología , Transexualidad/sangre , Transexualidad/psicología , Adulto JovenRESUMEN
STUDY QUESTION: Does hysteroscopic proximal tubal occlusion by intratubal devices as a treatment for hydrosalpinges result in comparable ongoing pregnancy rates following IVF/ICSI when compared with laparoscopic salpingectomy? SUMMARY ANSWER: Hysteroscopic proximal tubal occlusion by intratubal devices is inferior to laparoscopic salpingectomy in the treatment of hydrosalpinges in women undergoing IVF/ICSI with respect to ongoing pregnancy rates. WHAT IS KNOWN ALREADY: It is known that women with hydrosalpinges undergoing IVF have poorer pregnancy outcomes compared with women with other forms of tubal infertility. In these women, both laparoscopic salpingectomy and laparoscopic proximal tubal ligation are known to improve IVF outcomes. At present, it is unclear whether a less-invasive hysteroscopic treatment with intratubal devices leads to similar ongoing pregnancy rates following IVF when compared with laparoscopic salpingectomy. STUDY DESIGN, SIZE, DURATION: A two-centre, randomized, controlled, non-inferiority trial. Between October 2009 and December 2014 a total of 85 women were included in this study; of whom, 42 were randomized to hysteroscopic proximal occlusion by intratubal device placement and 43 were randomized to laparoscopic salpingectomy. Randomization was based on a computer-generated randomization list. The study was unblinded. The primary outcome was ongoing pregnancy rate, defined as a fetal heartbeat on ultrasound beyond 10-week gestation following one IVF/ICSI treatment (fresh and frozen-thawed embryo transfers). PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied women aged 18-41 years, with uni- or bilateral ultrasound visible hydrosalpinges who were scheduled for an IVF/ICSI treatment. MAIN RESULTS AND THE ROLE OF CHANCE: The ongoing pregnancy rates per patient according to the intention-to-treat principle were 11/42 (26.2%) after hysteroscopic proximal occlusion by intratubal devices (intervention group) versus 24/43 (55.8%) after laparoscopic salpingectomy (control group) (P = 0.008) [absolute difference: 26.1%; 95% confidence interval (CI): 0.5-51.7, relative risk (RR): 0.56; 95% CI: 0.31-1.03, P = 0.01]. In the per protocol analysis, the ongoing pregnancy rate per patient following hysteroscopic proximal occlusion by intratubal devices was 9/27 (33.3%) compared with 19/32 (59.4%) following laparoscopic salpingectomy (P = 0.067) (absolute difference: 29.6%; 95% CI: 7.1 to 49.1, RR: 0.47; 95% CI: 0.27-0.83, P = 0.062). LIMITATIONS, REASONS FOR CAUTION: Masking participants and investigators would be difficult due to the nature of both interventions. Since we had objective outcome measurements, we withheld sham procedures, leaving the study unblinded. Furthermore, our low sample size resulted in wide CIs. A larger sample size would result in a more accurate treatment effect; however, this was non-feasible for recruitment and inclusion. WIDER IMPLICATIONS OF THE FINDINGS: In the treatment of hydrosalpinges prior to IVF/ICSI, hysteroscopic proximal occlusion by intratubal devices is inferior to laparoscopic salpingectomy. STUDY FUNDING/COMPETING INTERESTS: The intratubal devices were received from Conceptus, Inc., San Carlos, CA, USA, which was acquired by Bayer HealthCare Pharmaceuticals, Inc., Whippany, NJ, USA in 2013. Conceptus, Inc./Bayer HealthCare Pharmaceuticals, Inc. had no role in the study design, data collection and analyses, decision to publish or preparation of the manuscript. The study as a whole was funded by the SWOG (foundation for scientific investigation in obstetrics and gynaecology of the VU University Medical Centre, Amsterdam, the Netherlands). P.G.A.H. has received non-financial support from Conceptus, Inc. during the conduct of this study. He has received grants from Ferring B.V., Merck Serono and Abbott outside the submitted work. M.H.E. has received personal fees from Smith and Nephew and IQ Medical Ventures outside the submitted work. TRIAL REGISTRATION NUMBER: The Dutch Trial Register: NTR 2073. TRIAL REGISTRATION DATE: October 21, 2009. DATE OF FIRST PATIENT'S ENROLMENT: October 26, 2009.
Asunto(s)
Enfermedades de las Trompas Uterinas/cirugía , Fertilización In Vitro/métodos , Salpingectomía/métodos , Inyecciones de Esperma Intracitoplasmáticas/métodos , Esterilización Tubaria/métodos , Adolescente , Adulto , Enfermedades de las Trompas Uterinas/diagnóstico por imagen , Femenino , Humanos , Embarazo , Resultado del Embarazo , Índice de Embarazo , Resultado del Tratamiento , Adulto JovenRESUMEN
STUDY QUESTION: Which reproductive endocrine changes are attributed exclusively to laparoscopic ovarian drilling in polycystic ovarian syndrome (PCOS)? SUMMARY ANSWER: Laser evaporation-specific endocrine effects were the prevention of an immediate increase in inhibin B and a sustained decrease in testosterone, androstenedione and anti-Müllarian hormone (AMH). WHAT IS KNOWN ALREADY: All ovarian drilling procedures result in reproductive endocrine changes. It is not known which of these changes are the result of ovarian drilling and which are related to the surgery per se. STUDY DESIGN, SIZE, DURATION: This prospective controlled study was performed at an outpatient academic fertility clinic. Between 2007 and 2010, a total of 21 oligo- or amenorrheic PCOS patients were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: Included were oligo- or amenorrheic PCOS patients with all three of the Rotterdam criteria and luteinizing hormone (LH) >6.5 U/l. All PCOS patients had an indication for diagnostic surgery due to subfertility. There were 12 PCOS patients who chose to undergo ovarian laser evaporation (CO2 laser, 25 W, 20 times/ovary) and 9 PCOS who chose a diagnostic laparoscopy only (controls). Reproductive endocrinology was measured before, and until 5 days after, surgery, and four gonadotrophin-releasing hormone (GnRH) 'double pulse' tests were included. The main outcome measures were changes in reproductive endocrinology and pituitary sensitivity/priming to GnRH after laser evaporation compared with diagnostic laparoscopy only. MAIN RESULTS AND THE ROLE OF CHANCE: In the first hours after surgery, both groups showed an increase in LH, follicle stimulating hormone, estrogen and a decrease in testosterone, androstenedione, AMH and insulin growth factor-1 (P < 0.05). Inhibin B increased in the laparoscopy only group (P < 0.05). In the first days after surgery, testosterone, androstenedione and AMH remained at lower than baseline levels exclusively in the laser group (P < 0.05). Pituitary sensitivity/priming to GnRH was not altered after either laser evaporation or laparoscopy only. LIMITATIONS, REASONS FOR CAUTION: The limitations of this study are the short follow-up period and the relatively small groups. WIDER IMPLICATIONS OF THE FINDINGS: The strength of this study is the integrally measured endocrine profiles in combination with an optimal control group of PCOS patients undergoing diagnostic laparoscopy only. Interestingly, most of the immediate endocrine changes after laser evaporation could be related to the surgical context and not to the ovarian drilling procedure itself. STUDY FUNDING/COMPETING INTERESTS: The study was funded by the Foundation of Scientific Research in Obstetrics and Gynaecology and the study medication, Lutrelef, was donated by Ferring, The Netherlands, Hoofdorphe There were no conflicts of interests mentioned by the authors.
Asunto(s)
Hormona Folículo Estimulante/sangre , Laparoscopía , Terapia por Láser , Hormona Luteinizante/sangre , Síndrome del Ovario Poliquístico/sangre , Adulto , Estradiol/sangre , Femenino , Humanos , Síndrome del Ovario Poliquístico/diagnóstico , Síndrome del Ovario Poliquístico/cirugía , Progesterona/sangre , Estudios Prospectivos , Testosterona/sangre , Resultado del TratamientoRESUMEN
STUDY QUESTION: What is the value of embryo selection by metabolomic profiling of culture medium with near-infrared (NIR) spectroscopy as an adjunct to morphology, compared with embryo selection by morphology alone, based on an individual patient data meta-analysis (IPD MA)? SUMMARY ANSWER: The IPD MA indicates that the live birth rate after embryo selection by NIR spectroscopy and morphology is not significantly different compared with the live birth rate after embryo selection by morphology alone. WHAT IS KNOWN ALREADY: Retrospective proof of principle studies has consistently shown that high NIR viability scores are correlated with a high implantation potential of embryos. However, randomized controlled trials (RCTs) have generally shown no benefit of the NIR technology over embryo morphology, although there have been some conflicting results between pregnancy outcomes on different days of embryo transfer. STUDY DESIGN, SIZE, DURATION: This IPD MA included all existing RCTs (n = 4) in which embryo selection by morphology was compared with embryo selection by morphology and the use of NIR spectroscopy of spent embryo culture medium by the Viametrics-E(™). PARTICIPANTS/MATERIALS, SETTING, METHODS: Searches of PubMed, the Cochrane Library and the WHO International Clinical Trials Registry were conducted and the sole manufacturer of the Viametrics-E(™) was consulted to identify clinics where an RCT comparing embryo selection by morphology to embryo selection by morphology and the use of the Viametrics-E(™) (NIR viability score) was performed. A total of 20 citations were potentially eligible for inclusion, two of which met the inclusion criteria. The manufacturer of the Viametrics-E(™) provided two additional clinical sites of use. In total, four RCTs were identified as eligible for inclusion. The IPD MA was based on a fixed effect model due to the lack of heterogeneity between included studies. Differences between study groups were tested and reported using logistic regression models adjusted for significant confounders. The pooled analysis of the primary outcome led to a total sample size of 924 patients: 484 patients in the control group (embryo selection by morphology alone) and 440 patients in the treatment group (embryo selection by morphology plus NIR spectroscopy). MAIN RESULTS AND THE ROLE OF CHANCE: The live birth rates in the control group and the NIR group were 34.7% (168 of 484) and 33.2% (146 of 440), respectively. The pooled odds ratio (OR) was 0.98 [95% confidence interval (CI) 0.74-1.29], indicating no difference in live birth rates between the two study groups. The data of the four studies showed no significant heterogeneity (I(2) = 26.2% P = 0.26). The multivariate regression analysis including all confounders show that maternal age (OR 0.90, 95% CI 0.87-0.94) and the number of previous IVF cycles (OR 0.83, 95% CI 0.71-0.96) were significantly related to live birth. The study group (i.e. embryo selection by morphology or embryo selection by morphology plus NIR) was not related to live birth (OR 0.97, 95% CI 0.73-1.29). LIMITATIONS AND REASONS FOR CAUTION: The availability of at least two similar best quality embryos as an inclusion criterion prior to transfer in the two largest RCTs might have caused a selection bias towards a better prognosis patient group. WIDER IMPLICATIONS OF THE FINDINGS: There is at present no evidence that NIR spectroscopy of spent embryo culture media in its current form can be used in daily practice to improve live birth rates.
Asunto(s)
Medios de Cultivo/química , Transferencia de Embrión/métodos , Nacimiento Vivo , Metabolómica , Tasa de Natalidad , Femenino , Fertilización In Vitro/métodos , Humanos , Embarazo , Resultado del Embarazo , Índice de Embarazo , Estudios Retrospectivos , Espectroscopía Infrarroja Corta/métodosRESUMEN
STUDY QUESTION: What is the effectiveness of continued treatment with clomiphene citrate (CC) in women with World Health Organization (WHO) type II anovulation who have had at least six ovulatory cycles with CC but did not conceive? SUMMARY ANSWER: When women continued CC after six treatment cycles, the cumulative incidence rate of the ongoing pregnancy rate was 54% (95% CI 37-78%) for cycles 7-12. WHAT IS KNOWN ALREADY: If women with WHO type II anovulation fail to conceive with CC within six ovulatory cycles, guidelines advise switching to gonadotrophins, which have a high risk of multiple gestation and are expensive. It is however not clear what success rate could be achieved by continued treatment with CC. STUDY DESIGN, SIZE, DURATION: We performed a retrospective cohort study of women with WHO II anovulation who visited the fertility clinics of five hospitals in the Netherlands between 1994 and 2010. We included women treated with CC who had had at least six ovulatory cycles without successful conception (n = 114) after which CC was continued using dosages varying from 50 to 150 mg per day for 5 days. PARTICIPANTS/MATERIALS, SETTING, METHODS: Follow-up was a total of 12 treatment cycles. Primary outcome was the cumulative incidence rate of an ongoing pregnancy at the end of treatment. MAIN RESULTS AND THE ROLE OF CHANCE: We recruited 114 women that had ovulated on CC for at least six cycles but had not conceived. Of these 114 women, 35 (31%) had an ongoing pregnancy resulting in a cumulative incidence rate of an ongoing pregnancy of 54% after 7-12 treatment cycles with CC. LIMITATIONS, REASONS FOR CAUTION: Limitations of our study are its retrospective approach. WIDER IMPLICATIONS OF THE FINDINGS: Randomized trials comparing continued treatment with CC with the relatively established second line treatment with gonadotrophins are justified. In the meantime, we suggest to only begin this less convenient and more expensive treatment for women who do not conceive after 12 ovulatory cycles with CC. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: Not applicable.
Asunto(s)
Clomifeno/uso terapéutico , Fármacos para la Fertilidad Femenina/uso terapéutico , Inducción de la Ovulación/métodos , Adulto , Clomifeno/administración & dosificación , Bases de Datos Factuales , Esquema de Medicación , Femenino , Fármacos para la Fertilidad Femenina/administración & dosificación , Humanos , Embarazo , Índice de Embarazo , Estudios RetrospectivosRESUMEN
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.
Asunto(s)
Fertilización In Vitro/estadística & datos numéricos , Modelos Económicos , Impuestos/estadística & datos numéricos , Contabilidad/métodos , Análisis Costo-Beneficio , Femenino , Fertilización In Vitro/efectos adversos , Humanos , Masculino , Países BajosRESUMEN
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.
Asunto(s)
Inseminación Artificial/métodos , Adulto , Femenino , Estudios de Seguimiento , Humanos , Inmovilización , Masculino , Embarazo , Resultado del Embarazo , Índice de EmbarazoRESUMEN
STUDY QUESTION: Can mixture survival models help distinguish infertility from subfertility in couples with an unexplained unfulfilled child wish? SUMMARY ANSWER: Mixture models estimated that 47% of the couples were infertile; female age and previous pregnancy were significantly related to infertility, whereas duration of child wish was associated with a longer time to pregnancy for subfertile couples. WHAT IS KNOWN ALREADY: To differentiate between couples who require assisted conception and couples who still have good chances of natural, i.e. unassisted, conception, several prediction models of natural conception have been developed. Prognostic factors in these models are usually assessed by Cox proportional hazard models that cannot differentiate between couples with an unfulfilled child wish who are subfertile, i.e. have reduced ability to conceive naturally, and couples who are really infertile, i.e. are completely unable to conceive naturally. We evaluated whether a mixture survival model can make such a distinction. STUDY DESIGN, SIZE, DURATION: Consecutive couples presenting at the fertility clinics of 38 centres in the Netherlands between January 2002 and February 2004 joined a prospective cohort study. Of the 7860 couples in the cohort, 3917 couples met our inclusion criteria. The median follow-up was 219 days, with a maximum of 5 years. PARTICIPANTS, SETTING, METHODS: Couples had to present with an unexplained cause of an unfulfilled child wish. A mixture model was used to estimate the proportion of couples who were infertile and the time to pregnancy for the subfertile couples. MAIN RESULTS AND THE ROLE OF CHANCE: During the follow-up, 794 couples conceived naturally. The mixture model estimated that 47% [95% confidence interval (CI): 33-56%] of couples were infertile, despite the absence of objective factors indicating a cause for infertility. Of the evaluated prognostic factors, female age, duration of child wish, previous pregnancy, semen quality, BMI and cycle length, female age [odds ratio (OR): 1.11, 95% CI: 1.03-1.19] and previous pregnancy (0.22, 95% CI: 0.07-0.67) were significant predictors of infertility. Among subfertile couples, a longer duration of a child wish (FFR: 0.72, 95% CI: 0.61-0.85) was a significant prognostic factor for time to pregnancy. In the Cox models, all variables except BMI were significant predictors of time to pregnancy. LIMITATIONS, REASONS FOR CAUTION: The mixture model had limited power due to a low number of couples at the end of the follow-up period. Mixture model analyses on external, long-term follow-up data are necessary to validate our results. WIDER IMPLICATIONS OF THE FINDINGS: Mixture models could be a useful tool in selecting couples who require assisted reproductive technology because the effects of prognostic factors can be subdivided into effects on the fraction of infertile couples and effects on the time to pregnancy for subfertile couples, which is not possible in conventional models. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grant 945/12/002 from ZonMw, the Netherlands Organization for Health Research and Development, The Hague, the Netherlands.
Asunto(s)
Composición Familiar , Objetivos , Infertilidad Femenina/diagnóstico , Infertilidad Masculina/diagnóstico , Adulto , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Infertilidad Femenina/fisiopatología , Infertilidad Femenina/psicología , Infertilidad Masculina/fisiopatología , Infertilidad Masculina/psicología , Masculino , Modelos Biológicos , Países Bajos , Valor Predictivo de las Pruebas , Embarazo , Pronóstico , Estudios Prospectivos , Análisis de Semen , Índice de Severidad de la Enfermedad , Factores de Tiempo , Tiempo para Quedar EmbarazadaRESUMEN
STUDY QUESTION: Does preconceptionally started low-dose aspirin prevent hypertensive pregnancy complications and preterm delivery in IVF patients? SUMMARY ANSWER: The current data do not support the use of preconceptionally started low-dose aspirin treatment for the prevention of hypertensive pregnancy complications and preterm delivery in IVF women. WHAT IS KNOWN ALREADY: Studies starting low-dose aspirin treatment as prevention in the second trimester of pregnancy found no or only moderate reductions in the relative risk of developing pre-eclampsia. Low-dose aspirin was possibly started too late, that is after the first episode of trophoblast invasion. STUDY DESIGN, SIZE, DURATION: We performed a meta-analysis with individual patient data (IPD), in which four authors could provide IPD on a total of 268 pregnancies (n = 131 treated with aspirin, n = 137 placebo). Data on hypertensive pregnancy complications and preterm delivery were collected. PARTICIPANTS/MATERIALS, SETTING, METHODS: All separate databases were merged into a summary database. Treatment effect of aspirin on the incidence of hypertensive pregnancy complications (n = 187) and preterm delivery (n = 180) were estimated with odds ratios (OR) and 95% confidence intervals (95% CI) using multivariable logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: There were significantly fewer twin pregnancies in the aspirin group (OR 0.55 95% CI 0.30-0.98), but no significant differences for hypertensive pregnancy complications and preterm delivery: for singletons OR 0.62 (95% CI 0.22-1.7) and OR 0.52 (95% CI 0.16-1.7), respectively, as well as for twin pregnancies OR 1.2 (95% CI 0.35-4.4) and OR 1.6 (95% CI 0.51-5.0), respectively. LIMITATIONS, REASONS FOR CAUTION: We have to bear in mind that the included studies showed clinical heterogeneity; there was variation in the duration of low-dose aspirin therapy and degree of hypertension between the different studies. Although we combined IPD from four studies, we have to realize that the studies were not powered for the outcome of the current IPD meta-analysis. WIDER IMPLICATIONS OF THE FINDINGS: Based on the current meta-analysis with IPD we found no confirmation for the hypothesis that preconceptionally started low-dose aspirin reduces the incidence of hypertensive pregnancy complications or preterm delivery in IVF women. Larger studies are warranted.
Asunto(s)
Aspirina/uso terapéutico , Hipertensión Inducida en el Embarazo/prevención & control , Nacimiento Prematuro/prevención & control , Adulto , Aspirina/administración & dosificación , Femenino , Fertilización In Vitro/efectos adversos , Humanos , Modelos Logísticos , Oportunidad Relativa , Atención Preconceptiva , Embarazo , Embarazo Gemelar , Medición de RiesgoRESUMEN
STUDY QUESTION: Does the addition of exogenous LH to an IVF/ICSI stimulation protocol with recombinant FSH (r-FSH) and a GnRH antagonist improve the ovarian response and pregnancy rates in women of 35 years and older? SUMMARY ANSWER: Supplementation of LH during the second half of the follicular phase has no effect on pregnancy rates, implantation rates or on ovarian response in women of 35 years and older undergoing GnRH antagonist IVF/ICSI cycles. WHAT IS KNOWN ALREADY: In IVF/ICSI stimulation protocols GnRH agonists or antagonists are administered to prevent a premature pituitary LH surge, which can have a detrimental effect on the IVF/ICSI procedure. In effect, GnRH analogues cause the levels of both gonadotrophins to drop. In order to allow follicle growth FSH is administered exogenously, whereas LH is usually not supplemented. Although GnRH analogues prevent LH surges, there is evidence that, particularly in older women, administration of GnRH analogues may cause endogenous LH levels to decrease excessively. Several studies have been performed to investigate whether the addition of recombinant LH (r-LH) to r-FSH improves cycle outcome. Only a few studies have analysed this issue in the GnRH antagonist protocol and the results of these trials obtained in older women (>35 years old) are conflicting. STUDY DESIGN, SIZE, DURATION: A multicentre RCT was performed between 2004 and 2010 in 253 couples who were undergoing IVF or ICSI. Women were 35 years or older and received ovarian stimulation in a protocol with r-FSH (Gonal-F 225 IU/day) starting from cycle day 3 and GnRH antagonist (Cetrotide 0.25 mg/day) from stimulation day 6. Randomization took place on stimulation day 6 to receive both r-FSH and r-LH (Luveris 150 IU/day) or continue with FSH alone. Randomization for r-LH supplementation was performed centrally by serially numbered, opaque, sealed envelopes, stratified by centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: Of 253 subjects randomized, 125 received both r-FSH and r-LH and 128 received r-FSH only. Patients were recruited from the Division of Reproductive Medicine of the Obstetrics and Gynaecology department of four hospitals in the Netherlands. MAIN RESULTS AND THE ROLE OF CHANCE: There were no demographic or clinical differences between the groups. The intention-to-treat analysis revealed that of those receiving both r-FSH and r-LH, 35 (28.0%) had a clinical pregnancy, compared with 38 (29.7%) receiving only r-FSH (mean difference -1.5%; 95% confidence interval (CI) -9.4 to 12.7, P = 0.9). Ongoing pregnancy rates were 25 (20%) versus 28 (21.9%) (mean difference -1.9%; 95% CI -8.2 to 11.9, P = 0.9) and implantation rates 18.8 versus 20.7% (mean difference -1.9%; 95% CI -8.0 to 11.7, P = 0.6) in the 'r-FSH and r-LH' and 'r-FSH only' groups respectively. LIMITATIONS, REASONS FOR CAUTION: A limitation of our study is its early closure. This was done because the interim analysis after randomization of 250 patients indicated no benefit in any aspect of the experiment. WIDER IMPLICATIONS OF THE FINDINGS: Given previous data, including a Cochrane review, and our own results the evidence indicates that LH supplementation has no benefit on ongoing pregnancy rates in women of 35 years or older. STUDY FUNDING/COMPETING INTEREST(S): Merck Serono Netherlands, an affiliate of Merck Serono SA- Geneva, an affiliate of Merck KGaA, Darmstadt, Germany has donated the r-LH (Luveris(®)). No conflict of interest to declare. TRIAL REGISTRATION NUMBER: The trial was registered in the Dutch trial register (ISRCTN10841210).
Asunto(s)
Fertilización In Vitro/métodos , Hormona Liberadora de Gonadotropina/análogos & derivados , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Hormona Luteinizante/farmacología , Adulto , Femenino , Hormona Liberadora de Gonadotropina/administración & dosificación , Hormona Liberadora de Gonadotropina/farmacología , Humanos , Modelos Logísticos , Hormona Luteinizante/administración & dosificación , Inducción de la Ovulación/métodos , Embarazo , Índice de EmbarazoRESUMEN
BACKGROUND: Prognostic models for natural conception help to identify subfertile couples with high chances of natural conception, who do not need fertility treatment yet. The use of such models and subsequent tailored expectant management (TEM) is not always practiced. Previous qualitative research has identified barriers and facilitators of TEM among patients and professionals. The aim of this study was to assess the prevalence of those barriers and facilitators and to evaluate which factors predict patients' appreciation of TEM and professionals' adherence to TEM. METHODS: We performed a nationwide survey. Based on the previously identified barriers and facilitators two questionnaires were developed and sent to 195 couples and 167 professionals. Multivariate analysis was performed to evaluate which factors predicted patients' appreciation of TEM and professional adherence to TEM. RESULTS: In total, 118 (61%) couples and 117 (70%) professionals responded and 96 couples and 117 professionals were included in the analysis. Patients' mean appreciation of TEM was 5.7, on a 10-point Likert scale. Patients with a lower appreciation of TEM had a higher need for patient information (P = 0.047). The professionals reported a mean adherence to TEM of 63%. Adherence to TEM was higher when professionals were fertility doctors (P = 0.041). Facilitators in the clinical domain were associated with a higher adherence to TEM (P = 0.091). Barriers in the professional domain had a negative impact on adherence to TEM (P = 0.008). CONCLUSIONS: The limited implementation of TEM is caused by both patient and professional-related factors. This study provides practical tools to improve the implementation of TEM.
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Técnicas de Apoyo para la Decisión , Infertilidad/diagnóstico , Adulto , Femenino , Personal de Salud , Humanos , Infertilidad/terapia , Masculino , Análisis Multivariante , Pronóstico , Técnicas Reproductivas Asistidas , Factores de TiempoRESUMEN
BACKGROUND: Dizygotic twin pregnancies after IVF treatment are the result of multiple embryos transferred into the uterine cavity, followed by successful double implantation. Factors that increase the chance of multiple implantation after IVF are relatively unknown. The present study aimed to investigate whether features of body composition, such as maternal height, weight and body mass index (BMI) are associated with an increased chance of dizygotic twinning after IVF with double embryo transfer (DET). METHODS: This study was conducted using data from a large Dutch nationwide cohort that comprised 19 861 women who had IVF or ICSI treatment between 1983 and 1995 (OMEGA study). First 'fresh' IVF and ICSI cycles with DET resulting in a delivery of a singleton or twin (living as well as stillborn) were selected. A multivariable logistic regression analysis was performed, with the delivery of a singleton or twin as the dependent variable and height, weight, BMI, maternal age, number of retrieved oocytes, use of alcohol, smoking, highest level of education and parity as independent variables. RESULTS: Of the 6598 women who completed their first IVF or ICSI cycle, 2375 had DET, resulting in 496 deliveries of 371 singletons and 125 twins. Multivariable regression analysis revealed that tall women (>1.74 cm) and women with a high number of retrieved oocytes (>8) had an increased chance of dizygotic twinning [OR: 1.8 (95% CI: 1.0-3.4) and OR: 2.2 (95% CI: 1.3-3.8), respectively]. CONCLUSIONS: Our data demonstrate that tall stature and increased number of retrieved oocytes independently increase the chance of dizygotic twinning after IVF with DET.
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Transferencia de Embrión/métodos , Embarazo Gemelar , Adulto , Estatura , Índice de Masa Corporal , Peso Corporal , Implantación del Embrión , Femenino , Fertilización In Vitro , Humanos , Modelos Logísticos , Análisis Multivariante , Embarazo , Estudios Retrospectivos , Factores de Riesgo , Gemelos DicigóticosRESUMEN
The position of transfer air bubbles after embryo transfer is related to the pregnancy rate. With the conventional manual embryo-transfer technique it is not possible to predict the final position of the air bubbles. This position mainly depends on the catheter load speed at transfer (injection speed), a parameter that remains uncontrollable with the conventional technique even after standardization of the protocol. Therefore, the development of an automated device that generates a standardized injection speed is desirable. This study aimed to examine the variation in injection speeds in manual embryo transfer and pump-regulated embryo transfer (PRET). Seven laboratory technicians were asked to perform simulated transfers using the conventional embryo-transfer technique. Their injection speeds were compared with that of a PRET device. The results indicate that in manually performed transfers, even after standardization of the protocol, there is still a large variation in injection speed, while a PRET device generates a reliable and reproducible injection speed and therefore brings new possibilities for further standardization of the embryo-transfer procedure. Future research should reveal whether these experiments mimic real clinical circumstances and if a standardized injection speed results in more exact positioning of the transferred embryos and therefore higher pregnancy rates.
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Transferencia de Embrión/métodos , Automatización , Catéteres/normas , Transferencia de Embrión/instrumentación , Femenino , Fertilización In Vitro , Humanos , Embarazo , Índice de Embarazo , Estándares de ReferenciaRESUMEN
OBJECTIVE: The current evidence concerning the best treatment option for couples with unexplained and male subfertility is inconclusive. Most studies that have evaluated the effectiveness of treatment options, such as expectant management (EM), intrauterine insemination (IUI), with or without controlled ovarian stimulation (COS), and in vitro fertilisation (IVF), have not taken the couples' prognosis into account. It is very likely that the individual prognosis of the couple influences the effect of treatment. Individual patient data analyses allow us to take these prognostic factors into account, and to evaluate their effect on treatment outcome. This study aims to use anonymised data from relevant published trials to perform an individual patient data meta-analysis, evaluating the effect of couples' prognosis on the effectiveness of EM, IUI, with or without COS, and IVF. METHODS: Based on earlier systematic reviews and an updated search, randomised controlled trials will be considered for inclusion. Untreated subfertile couples with unexplained or male subfertility included in trials comparing EM, IUI, with or without COS, and IVF are included. Authors of the included studies will be invited to share their original anonymised data. The data will be assessed on validity, quality and completeness. The prognosis of the individual couple will be calculated with existing prognostic models. The effect of the prognosis on treatment outcome will be analysed with marker-by-treatment predictiveness curves, illustrating the effect of prognosis on treatment outcome. This study is registered in PROSPERO (registration number CRD42011001832). CONCLUSION: Ultimately, this study may help to select the appropriate fertility treatment, tailored to the needs of an individual couple.
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Fertilización In Vitro/métodos , Infertilidad Femenina/terapia , Infertilidad Masculina/terapia , Inseminación Artificial/métodos , Inducción de la Ovulación/métodos , Femenino , Humanos , Masculino , Embarazo , Resultado del Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
BACKGROUND: Insulin resistance, i.e. impaired insulin-mediated glucose uptake (IMGU), is a major risk factor for type 2 diabetes in women with polycystic ovary syndrome (PCOS). Insulin-induced capillary recruitment (IICR) is considered a significant determinant of IMGU. We investigated whether IICR is a determinant IMGU in obese and lean women with and without PCOS. METHODS: The study included 36 women with PCOS (20 lean, BMI 21.9 ± 2.3 kg/m(2) and 16 obese, BMI 35.9 ± 6.0 kg/m(2)) and 27 age-matched healthy controls (14 lean, BMI 22.2 ± 1.8 kg/m(2) and 13 obese, BMI 40.5 ± 7.0 kg/m(2)). IICR was evaluated by capillary microscopy during an isoglycemic-hyperinsulinemic clamp. IMGU was expressed as M/I value. RESULTS: The M/I value was significantly lower in obese PCOS women compared with obese controls [0.5 (0.2-1.1) versus 0.8 (0.3-1.4) (mg kg(-1) min(-1) pmol l(-1)) × 100, P < 0.01], whereas the small difference between lean PCOS and lean control women was non-significant [1.5 (0.5-2.6) versus 1.7 (1.0-3.7) (mg kg(-1) min(-1) pmol l(-1)) × 100, P = 0.17]. Hyperinsulinemia increased capillary recruitment in lean controls (53.5 ± 20.3 versus 64.9 ± 27.4 n/mm(2), P < 0.05), but not in either PCOS group nor in obese controls. IICR and androgens were a determinant of M/I value only in lean women with or without PCOS. CONCLUSIONS: PCOS per se is associated with impaired IICR. Obese women with PCOS, in part independent of obesity, demonstrated a profound insulin resistance, whereas the difference between lean PCOS women and healthy controls was small and statistically non-significant. IICR was a determinant of IMGU in lean, but not in obese, women regardless of the presence of PCOS.
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Capilares/metabolismo , Insulina/metabolismo , Obesidad/metabolismo , Síndrome del Ovario Poliquístico/metabolismo , Adulto , Glucemia/metabolismo , Presión Sanguínea , Índice de Masa Corporal , Peso Corporal , Capilares/efectos de los fármacos , Femenino , Humanos , Resistencia a la Insulina , Microcirculación , Modelos EstadísticosRESUMEN
INTRODUCTION: Prediction models for spontaneous pregnancy are useful tools to prevent overtreatment, complications and costs in subfertile couples with a good prognosis. The use of such models and subsequent expectant management in couples with a good prognosis are recommended in the Dutch fertility guidelines, but not fully implemented. In this study, we assess risk factors for non-adherence to tailored expectant management. METHODS: Couples with mild male, unexplained and cervical subfertility were included in this multicentre prospective cohort study. If the probability of spontaneous pregnancy within 12 months was ≥40%, expectant management for 6-12 months was advised. Multivariable logistic regression was used to identify patient and clinical characteristics associated with non-adherence to tailored expectant management. RESULTS: We included 3021 couples of whom 1130 (38%) had a ≥40% probability of a spontaneous pregnancy. Follow-up was available for 1020 (90%) couples of whom 214 (21%) had started treatment between 6 and 12 months and 153 (15%) within 6 months. A higher female age and a longer duration of subfertility were associated with treatment within 6 months (OR: 1.06, 95% CI: 1.01-1.1; OR: 1.4; 95% CI: 1.1-1.8). A fertility doctor in a clinical team reduced the risk of treatment within 6 months (OR: 0.62; 95% CI: 0.39-0.99). CONCLUSIONS: In couples with a favorable prognosis for spontaneous pregnancy, there is considerable overtreatment, especially if the woman is older and duration of the subfertility is longer. The presence of a fertility doctor in a clinic may prevent early treatment.
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Infertilidad/terapia , Técnicas Reproductivas Asistidas/estadística & datos numéricos , Femenino , Fertilización , Humanos , Infertilidad/diagnóstico , Modelos Logísticos , Masculino , Edad Materna , Análisis Multivariante , Países Bajos , Embarazo , Índice de Embarazo , Probabilidad , Pronóstico , Factores de Riesgo , Factores SocioeconómicosRESUMEN
BACKGROUND: Laparoscopy has been claimed to be superior to hysterosalpingography (HSG) in predicting fertility. Whether this conclusion is applicable to a general subfertile population can be questioned as data in support of this claim were collected in third line centres. The aim of this study was to assess the prognostic capacity of HSG and laparoscopy in a general subfertile population. METHODS: In 38 centres, we prospectively studied a cohort of patients referred for subfertility between 2002 and 2004, who underwent HSG and/or laparoscopy as part of their subfertility work-up. Follow-up started immediately after tubal testing and ended 12 months thereafter. Time to pregnancy was censored at the of date last contact, when the woman was not pregnant or at the start of treatment. Kaplan-Meier curves for the occurrence of spontaneous intrauterine pregnancy were constructed for patients without tubal pathology, for those with unilateral tubal pathology and for patients with bilateral tubal pathology at HSG or laparoscopy. Multivariable Cox regression analysis was used to calculate fecundity rate ratios (FRRs) to express associations between tubal pathology and the occurrence of an intrauterine pregnancy. RESULTS: Of the 3301 included patients, 2043 underwent HSG only, 747 underwent diagnostic laparoscopy only and 511 underwent both. At HSG, 322 (13%) patients showed unilateral tubal pathology and 135 (5%) showed bilateral tubal pathology. At laparoscopy, 167 (13%) showed unilateral tubal pathology and 215 (17%) showed bilateral tubal pathology. Multivariable analysis resulted in FRRs of 0.81 [95% confidence interval (CI): 0.59-1.1] for unilateral, and 0.28 (95% CI: 0.13-0.59) for bilateral, tubal pathology at HSG. The FRRs at laparoscopy were 0.85 (95% CI: 0.47-1.52) for unilateral, and 0.24 (95% CI: 0.11-0.54) for bilateral, tubal pathology. CONCLUSIONS: Patients with unilateral tubal pathology at HSG and laparoscopy had a moderate reduction in pregnancy chances, whereas those with bilateral tubal pathology at HSG and laparoscopy had a severe reduction in pregnancy chances. This reduction was similar for HSG and laparoscopy, suggesting that HSG and laparoscopy have a comparable predictive capacity for natural conception.