Gonadotrophins or clomiphene citrate in couples with unexplained infertility undergoing intrauterine insemination: a cost-effectiveness analysis.

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.

Uterine Artery Embolization Versus Hysterectomy in the Treatment of Symptomatic Adenomyosis: Protocol for the Randomized QUESTA Trial.

BACKGROUND: Adenomyosis is a benign uterine disease characterized by invasion of endometrium into the myometrium resulting in heavy menstrual bleeding and pain (dysmenorrhea). Hysterectomy is established as the final treatment option when conservative treatment fails. Uterine artery embolization (UAE) in patients with symptomatic adenomyosis has demonstrated to reduce symptoms and improve quality of life. However, randomized controlled trials are lacking. OBJECTIVE: With this study, we aim to evaluate the impact of UAE on Health-Related Quality of Life (HRQOL) in a randomized comparison to hysterectomy in patients with symptomatic adenomyosis. METHODS: This is a multicenter non-blinded randomized controlled trial comparing UAE and hysterectomy. Eligible patients are symptomatic premenopausal women without the desire to conceive and who have symptomatic magnetic resonance imaging (MRI)-confirmed pure adenomyosis or dominant adenomyosis accompanied by fibroids. After obtaining informed consent, patients will be randomly allocated to treatment in a 2:1 UAE versus hysterectomy ratio. The primary objective is HRQOL at 6 months following the assigned intervention. Secondary outcomes are technical results, pain management, clinical outcomes, HRQOL, and cost effectiveness during 2 years of follow-up. In addition, transvaginal ultrasound (TVUS) and MRI will be performed at regular intervals after UAE. RESULTS: Patient enrollment started November 2015. The follow-up period will be completed two years after inclusion of the last patient. At the time of submission of this article, data cleaning and analyses have not yet started. CONCLUSIONS: This trial will provide insight for caretakers and future patients about the effect of UAE compared to the gold standard hysterectomy in the treatment of symptomatic adenomyosis and is therefore expected to improve patients' wellbeing and quality of life. TRIAL REGISTRATION: Netherlands Trial Register NTR5615; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5615 (Archived by WebCite at http://www.webcitation.org/6xZRyXeIF).

Pre-treatment with GnRHa or ulipristal acetate prior to laparoscopic and laparotomic myomectomy: A systematic review and meta-analysis.

BACKGROUND: Myomectomy has potential risks of complications. To reduce these risks, medical pre-treatment can be applied to reduce fibroid size and thereby potentially decrease intra-operative blood loss, the need for blood transfusion and emergency hysterectomy. The aim of this systematic review and meta-analysis is to study the effectiveness of medical pre-treatment with Gonadotropin-releasing hormone agonists (GnRHa) or ulipristal acetate prior to laparoscopic or laparotomic myomectomy on intra-operative and post-operative outcomes. METHODS: We performed an extensive search in Embase.com, Wiley/Cochrane Library and PubMed in accordance with the Prisma guidelines. All studies published as full papers in peer reviewed journals using GnRHa or ulipristal acetate as medical pre-treatment independent of route of administration or dosage before laparotomic or laparoscopic myomectomy were included. The primary outcome was duration of surgery. Secondary outcomes were duration of enucleation, blood loss, degree of difficulty of surgery, identification of cleavage planes, proportion of vertical incisions, conversion rate, frequency of blood transfusions, post-operative complications, duration of hospital stay, frequency of recurrence of fibroids, frequency of uterine adhesions, recovery time and quality of life. No language restrictions were applied. Meta-analysis were performed where possible. FINDINGS: Twenty-three studies were included. In laparotomic myomectomy, pre-treatment with GnRHa decreases intra-operative blood loss with 97.39ml (95% CI -111.80 to -82.97) compared to no pre-treatment or placebo. Pre-treatment with GnRHa before laparoscopic myomectomies also shows a reduction in intra-operative blood loss by 23.03ml (95% CI -40.79 to -5.27) and in the frequency of blood transfusions (OR 0.17, 95% CI 0.05 to 0.55) compared to no pre-treatment. Only two retrospective cohort studies reported on pre-treatment with ulipristal acetate compared to no pre-treatment before laparoscopic myomectomy showing a statistically significant reduction in intra-operative blood loss, duration of surgery and frequency of blood transfusions after pre-treatment with ulipristal acetate. CONCLUSION: Administration of GnRHa prior to laparotomic myomectomy reduces blood loss and might decrease uterine adhesion formation. Pre-treatment with GnRHa before laparoscopic myomectomy reduces blood loss, the frequency of blood transfusions and might increase recurrence rate of fibroids, however it should be taken into account that some results are mainly based on cohort studies. Other pre-treatment agent ulipristal acetate has not been investigated sufficiently for relevant surgical outcomes.

[The usefulness of evaluating effectiveness: pre-implantation genetic screening as an example]. / Het nut van effectiviteitsonderzoek: preïmplantatie genetische screening als voorbeeld.

Many treatments are applied in medical practice without a proper evaluation of their effectiveness. In this article, the possible negative consequences of such interventions are illustrated by using pre-implantation genetic screening (PGS) as an example. Research has shown that PGS is both expensive and ineffective. Hypothetically speaking, the non-performance of PGS saved 6 million euro in 2006 and the loss of 369 pregnancies was prevented. The investment in this research was much less than these 6 million euro saved. We postulate making the reimbursement of interventions dependent on their clinical effectiveness, and to use the money saved by this strategy for well-designed and well-executed research on the effectiveness of other interventions.

Perspectives of couples with high risk of transmitting genetic disorders.

OBJECTIVE: To investigate the preference for preimplantation genetic diagnosis (PGD) as an alternative to prenatal diagnosis (PND) in a large group of couples representing a wide array of genetic disorders. We also investigated the couple's familiarity with PGD and presented time trade-off scenarios for PGD versus PND, as PGD treatment is regularly accompanied by waiting lists. DESIGN: Questionnaire study. SETTING: Patient organizations representing genetic disorders. PATIENT(S): A total of 210 couples carrying genetic disorders. MAIN OUTCOME MEASURE(S): Preference for PGD or PND and familiarity with PGD in carrier couples. RESULT(S): Fifteen organizations representing 38 genetic disorders agreed to participate. Nine hundred eighty-three couples responded. In total 210 couples were in their reproductive years (women 18-40 years) and had a desire to conceive. Ninety couples (42%) had never heard of PGD. After they were informed, 127 couples (60%) wanted to have diagnostic testing (PND or PGD) performed. Ninety-four (74%) of these couples preferred testing with PGD. When no waiting list was used 102 couples (80%) preferred PGD. With a 2-year waiting list for PGD, 58 couples (46%) would opt for PGD. CONCLUSION(S): Many carrier couples are unaware of the existence of PGD. When informed, most couples prefer PGD more than PND. The preference for PGD decreases with longer waiting lists.

No beneficial effect of preimplantation genetic screening in women of advanced maternal age with a high risk for embryonic aneuploidy.

BACKGROUND: Human preimplantation embryos generated through in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatments show a variable rate of numerical chromosome abnormalities or aneuploidies. Preimplantation genetic screening (PGS) has been designed to screen for aneuploidies in high risk patients, with the aim of improving live birth rates in IVF/ICSI. We assessed whether the effect of PGS on live births rates differs in women of advanced maternal age with variable risks for embryonic aneuploidy, and weighed these effects against the results obtained after IVF/ICSI without PGS. METHODS: The effect of PGS on live birth rates was compared between groups defined by maternal age, number of previous miscarriages, semen quality, total amount of recombinant FSH (rFSH) administered during ovarian stimulation and total number of top-quality embryos, using data from a randomized controlled trial among women of advanced maternal age (35-41 years). RESULTS: There was no significant differential effect of PGS in groups based on maternal age (P-value of interaction 0.16), the number of previous miscarriages (P-value of interaction 0.93), semen quality (P-value of interaction 0.26), rFSH dose (P-value of interaction 0.15) or the number of top-quality embryos (P-value of interaction 0.59). Live birth rates after IVF/ICSI with PGS were lower in all groups when compared with live birth rates after IVF/ICSI without PGS. CONCLUSIONS: The paradigm that the effect of PGS is determined by a woman's risk for embryonic aneuploidy seems incorrect. In fact, PGS has no clinical benefit over standard IVF/ICSI in women of advanced maternal age regardless of their risk for embryonic aneuploidy.

In vitro fertilization with preimplantation genetic screening.

BACKGROUND: Pregnancy rates in women of advanced maternal age undergoing in vitro fertilization (IVF) are disappointingly low. It has been suggested that the use of preimplantation genetic screening of cleavage-stage embryos for aneuploidies may improve the effectiveness of IVF in these women. METHODS: We conducted a multicenter, randomized, double-blind, controlled trial comparing three cycles of IVF with and without preimplantation genetic screening in women 35 through 41 years of age. The primary outcome measure was ongoing pregnancy at 12 weeks of gestation. The secondary outcome measures were biochemical pregnancy, clinical pregnancy, miscarriage, and live birth. RESULTS: Four hundred eight women (206 assigned to preimplantation genetic screening and 202 assigned to the control group) underwent 836 cycles of IVF (434 cycles with and 402 cycles without preimplantation genetic screening). The ongoing-pregnancy rate was significantly lower in the women assigned to preimplantation genetic screening (52 of 206 women [25%]) than in those not assigned to preimplantation genetic screening (74 of 202 women [37%]; rate ratio, 0.69; 95% confidence interval [CI], 0.51 to 0.93). The women assigned to preimplantation genetic screening also had a significantly lower live-birth rate (49 of 206 women [24%] vs. 71 of 202 women [35%]; rate ratio, 0.68; 95% CI, 0.50 to 0.92). CONCLUSIONS: Preimplantation genetic screening did not increase but instead significantly reduced the rates of ongoing pregnancies and live births after IVF in women of advanced maternal age. (Current Controlled Trials number, ISRCTN76355836 [controlled-trials.com].).

Preferences of subfertile women regarding elective single embryo transfer: additional in vitro fertilization cycles are acceptable, lower pregnancy rates are not.

With identical pregnancy rates after elective single embryo transfer (ET) and double ET strategies consisting of three cycles of IVF or intracytoplasmic sperm injection (ICSI) plus transfers of thawed/frozen embryos if available, 46% of the women undergoing IVF/ICSI favor elective single ET. If elective single ET lowers pregnancy chances with 1%, 3%, or 5%, the percentage of women preferring elective single ET drops to 34%, 24%, and 15%, respectively. If four, five, or six cycles with elective single ET are needed to match the success rate of three cycles with double ET, the percentage of women with a preference for elective single ET drops from 46% to 40%, 36%, and 35% respectively.

Preimplantation genetic screening as an alternative to prenatal testing for Down syndrome: preferences of women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment.

OBJECTIVE: Although the primary goal of preimplantation genetic screening (PGS) is to increase pregnancy rates in women undergoing IVF/intracytoplasmic sperm injection treatment, it has been suggested that it may also be used as an alternative to prenatal testing for Down syndrome. DESIGN: Trade-off questionnaires. SETTING: Two university centers for reproductive medicine. PATIENT(S): Two hundred forty-four subfertile women. INTERVENTION(S): Scenarios with different pregnancy chances after PGS and with different risk reductions of a Down syndrome pregnancy were presented. MAIN OUTCOME MEASURE(S): Willingness to have PGS performed in the various scenarios. RESULT(S): In case PGS would discover all Down syndrome embryos without affecting pregnancy chances, 83% of the women would have PGS performed. If PGS lowered pregnancy chances from one in five to one in seven, 36% of the women preferred to have PGS performed. If PGS reduced the chance of a Down syndrome pregnancy with 80% without affecting pregnancy chances, 75% of the women would have PGS performed, and 31% of them would refrain from prenatal testing afterward. CONCLUSION(S): Most women favor PGS for Down syndrome screening, even if it is not 100% sensitive. The acceptability depends on the effect PGS has on pregnancy chances, and, to a lower extent on its sensitivity to detect Down syndrome embryos.