Effectiveness of recombinant human FSH: recombinant human LH combination treatment versus recombinant human FSH alone for assisted reproductive technology in women aged 35-40 years.

RESEARCH QUESTION: According to real-world data, is recombinant human FSH (r-hFSH) combined with recombinant human LH (r-hLH) or r-hFSH alone more effective for women of advanced maternal age (AMA) in terms of live birth? DESIGN: Non-interventional study comparing the effectiveness of r-hFSH and recombinant r-hLH (2:1 ratio) versus r-hFSH alone for ovarian stimulation during ART treatment in women aged 35-40 years, using real-world data from the Deutsches IVF-Register. RESULTS: Overall clinical pregnancy (29.8%, 95% CI 28.2 to 31.6 versus 27.8%, 95% CI 26.5 to 29.2) and live birth (20.3%, 95% CI 18.7 to 21.8 versus 18.0%, 95% CI 16.6 to 19.4) rates were not significantly different between the combined r-hFSH and r-hLH group and the r-hFSH alone group (P = 0.269 and P = 0.092, respectively). Treatment effect was significantly higher for combined r-hFSH and r-hLH compared with r-hFSH alone for clinical pregnancy (33.1%, 95% CI 31.0 to 35.0 versus 28.5%, 95% CI 26.6 to 30.4; P = 0.001, not adjusted for multiplicity) and live birth (22.5%, 95% CI 20.5 to 24.2 versus 19.4%, 95% CI 17.6 to 20.9; P = 0.014, not adjusted for multiplicity) in a post-hoc analysis of women with five to 14 oocytes retrieved (used as a surrogate for normal ovarian reserve), highlighting the potential benefits of combined r-hFSH and r-hLH for ovarian stimulation in women aged 35-40 years with normal ovarian reserve. CONCLUSIONS: Women of AMA with normal ovarian response benefit from treatment with combined r-hFSH and r-hLH in a 2:1 ratio versus r-hFSH alone in terms of live birth rate. The effectiveness of treatments is best assessed by RCTs; however, real-world data are valuable for examining the effectiveness of fertility treatment, especially among patient groups that are not well represented in clinical trials.

Assisted reproductive techniques in Latin America: the Latin American Registry 2016.

RESEARCH QUESTION: What was the utilization, effectiveness and perinatal outcome of assisted reproductive technologies (ART) performed in Latin America during 2016? DESIGN: Retrospective collection of multinational data on ART performed in 178 institutions from 15 Latin American countries. RESULTS: This paper reports on 85,474 initiated cycles, 15,070 deliveries and 18,182 babies born in this period. Of all fresh autologous IVF/intracytoplasmic sperm injection (ICSI) cycles, 40.9% were performed in women aged 35-39 years, and 31.1% in women aged ≥40 years. After removing freeze-all cycles, delivery rate per oocyte retrieval was 20.31% for ICSI and 21.85% for IVF. Fresh single embryo transfer including all age categories represented 22.96%, with a 15.35% delivery rate per transfer. Double embryo transfer represented 61.58% of transfers, with a 27.62% delivery rate per transfer. Multiple births included 18.12% twins and 0.55% triplets and higher. In oocyte donation, delivery rate per transfer was 32.89%, with a twin and triplet rate of 23.48% and 0.73%, respectively. Overall, preterm deliveries reached 17.11% in singletons, 65.69% in twins and 95.51% in triplets. Perinatal mortality was 8.0‰ in singletons, 19.0‰ in twins, and 62.3‰ in high-order multiples. CONCLUSIONS: The number of initiated cycles continues to increase. Compared with previous years, the number of embryos transferred decreased while the proportion of single embryo transfers increased with a drop in multiple births. It is vital to motivate health care providers and consumers to continue this trend.

Assisted reproductive techniques in Latin America: the Latin American Registry, 2015.

RESEARCH QUESTION: What was the utilization, effectiveness and safety of assisted reproductive technologies (ART) performed in Latin American countries during 2015, and what were the regional trends? DESIGN: Retrospective collection of multinational data on assisted reproduction techniques (IVF and intracytoplasmic sperm injection [ICSI], frozen embryo transfer, oocyte donation, preimplantation genetic testing and fertility preservation), from 175 institutions in 15 Latin American countries. RESULTS: In total, 41.25% of IVF/ICSI cycles were performed in women aged 35-39 years, and 28.35% in women aged ≥40 years. After removing freeze-all cycles, delivery rate per oocyte retrieval was 21.39% for ICSI and 24.29% for IVF. Multiple births included 19.58% twins and 0.95% triplets and higher. In oocyte donation, delivery rate per transfer was 36.77%, with a twin and triplet rate of 27.65% and 1.06%, respectively. Overall, preterm deliveries reached 17.38% in singletons, 64.94% in twins and 98.41% in triplets. Perinatal mortality in 14,936 births and 18,391 babies born was 10.5 per 1000 in singletons, 17.9 per 1000 in twins, and 57.1 per 1000 in high-order multiples. Elective single embryo transfer represented 3.11% of fresh transfers, with a 31.78% delivery rate per transfer. Elective double embryo transfer represented 23.3% of transfers, with a 37.79% delivery rate per transfer. Out of 18,391 babies born, 63.22% were singletons, 34.4% twins, and 2.38% triplets and higher. CONCLUSIONS: Given the effect of multiple births on prematurity, morbidity and perinatal mortality, reinforcing the existing trend of reducing the number of embryos transferred remains mandatory.

The impact of endometriosis on the outcome of Assisted Reproductive Technology.

BACKGROUND: Endometriosis has been described to impair fertility through various mechanisms. However, studies evaluating the reproductive outcomes of women undergoing assisted reproductive technologies show controversial results. The aim of this study is to assess whether the reproductive outcome is impaired among women with endometriosis-associated infertility undergoing IVF. METHODS: A retrospective cohort study was performed, including women undergoing IVF reported by the Red Latinoamericana de Reproduccion Asistida (Redlara) registry, between January 2010 and December 2012. The study group included women with endometriosis-associated infertility, and the control group women with tubal factor, endocrine disorders or unexplained infertility. Women above 40 years, severe male factor and premature ovarian failure were excluded. The reproductive outcomes of between both groups were compared. The primary outcome was live birth. Secondary outcomes included clinical pregnancy, miscarriage, number of oocytes retrieved and number of fertilized oocytes. Outcomes were assessed after the first fresh IVF cycle, and were adjusted for age and number of embryos transferred. RESULTS: A total of 22.416 women were included (3.583 with endometriosis and 18.833 in the control group). Mean age of patients in the endometriosis group and control group was 34.86 (3.47) and 34.61 (3.91) respectively, p = 0.000. The mean number of oocytes retrieved were 8.89 (6.23) and 9.86 (7.02) respectively, p = 0.000. No significant differences were observed between groups in terms of live birth (odds ratio (OR) 1.032, p = 0.556), clinical pregnancy (OR 1.044, p = 0.428) and miscarriage rates (OR 1.049, p = 0.623). Women with endometriosis had significantly lower number of oocytes retrieved (incidence risk ratio (IRR) 0.917, 95% CI 0.895-0.940), however, the number of fertilized oocytes did not differ among the two groups when adjusting for the number of oocytes retrieved (IRR 1.003, p = 0.794). An age-stratified analysis was performed, and no differences were observed in the reproductive outcomes between groups for women aged under 35 and 35 to 40. CONCLUSIONS: Reproductive outcomes among women undergoing IVF and diagnosed with endometriosis-associated infertility do not differ significantly from women without the disease. Although women with endometriosis generate fewer oocytes, fertilization rate is not impaired and the likelihood of achieving a live birth is also not affected.

Assisted reproduction techniques in Latin America: the Latin American Registry, 2014.

Multinational data on assisted reproduction techniques (IVF and intractytoplasmic sperm injection [ICSI], frozen embryo transfer, oocyte donation, preimplantation genetic diagnosis and fertility preservation) were collected from 159 institutions in 15 Latin American countries. A total of 41.34% of IVF-ICSI cycles were conducted in women aged 35-39 years and 23.35% in women aged 40 years and older. After removing freeze-all cases, delivery rate per oocyte retrieval was 25.05% for ICSI and 27.41% for IVF. Multiple births included 20.78% twins and 0.92% triplets and over. In oocyte donation, twins reached 28.93% and triplets 1.07%. Preterm deliveries reached 16.4% in singletons, 55.02% in twins and 76% in triplets. Perinatal mortality in 18,162 births was 23 per 1000 in singletons, 35 per 1000 in twins, and 36 per 1000 in high-order multiples. Elective single embryo transfer represented 2.63% of fresh transfers, with a 32.15% delivery rate per transfer. Elective double embryo transfer represented 23.74% of transfers, with a 41.03% delivery rate per transfer; 11,373 babies (62.6%) were singletons; 6398 (35.2%) twins, and 391 (2.2%), triplets and more. Given the effect of multiple births on prematurity, morbidity and perinatal mortality, reinforcing the existing trend of reducing the number of embryos transferred is mandatory.

Assisted reproductive techniques in Latin America: the Latin American Registry, 2013.

Multinational data on assisted reproduction techniques undertaken in 2013 were collected from 158 institutions in 15 Latin American countries. Individualized cycle-based data included 57,456 initiated cycles. Treatments included autologous IVF and intracytoplasmic sperm injection (ICSI), frozen embryo transfers, oocyte donations. In autologous reproduction, 29.22% of women were younger than 35 years, 40.1% were 35-39 years and 30.6% were 40 years or older. Overall delivery rate per oocyte retrieval was 20.6% for ICSI and 25.4% for IVF. Multiple births included 20.7% for twins and 1.1% for triplets and over. In oocyte donations, twins reached 30% and triplets 1.4%. In singletons, pre-term births were 7.5%: 36.58% in twins and 65.52% in triplets. The relative risk for prematurity was 4.9 (95% CI 4.5 to 5.3) in twins and 8.7 (95% CI 7.6 to 10.0) in triplets and above. Perinatal mortality was 29.4 per 1000 in singletons, 39.9 per 1000 in twins and 71.6 per 1000 in high order multiples. Elective single embryo transfer represented only 2% of cycles, with delivery rate of 39.1% in women aged 34 years or less. Given the effect of multiple births and prematurity, it is mandatory to reduce the number of embryos transferred in the region.

Effect of embryo freezing on perinatal outcome after assisted reproduction techniques: lessons from the Latin American Registry of Assisted Reproduction.

Embryo cryopreservation is an integral part of assisted reproduction techniques; it allows the sequential transfer of all embryos, thus diminishing the risk of multiple pregnancies and associated perinatal complications. To address concerns about the safety of this procedure, neonatal outcome after 43,070 fresh embryo transfers was compared with 12,068 frozen-thawed embryo transfers (FET). After adjusting for maternal age, gestational age, embryo development at time of transfer, number of babies born and gestational order, FET was not found to be associated with an increase in perinatal mortality (odds ratio [OR] 1.72, 95% confidence interval [CI] 0.81 to 3.62); preterm birth (OR 1.05, 95% CI 0.93 to 1.18); or extreme preterm birth (OR 0.82, 95% CI 0.64 to 1.06). Furthermore, after correcting for known confounding factors, FET was found to be associated with an increase in neonatal weight of 39.7 g (95% CI 1.54 to 64.10; P < 0.0001). Embryo cryopreservation was, therefore, not associated with an increase in the risk of poor perinatal outcome.

Assisted reproductive technologies in Latin America: the Latin American Registry, 2012.

Multinational data on assisted reproduction technologies were collected from 155 institutions in 14 Latin American countries during 2012. Case-by-case data included 47,326 assisted reproduction technology cycles covering over 80% of cycles carried out in Latin America. Treatments included IVF, intracytoplasmic sperm injection (ICSI), frozen embryo transfers, oocyte donations and fertility preservation. Embryo transfer and IVF-ICSI was carried out in 39% of women aged 35-39 years and 31% of women aged 40 years or over. Delivery rate per oocyte retrieval was 20.9% for ICSI and 26.5% for IVF. Multiple births comprised 20.6% twins and 1.2% triplets and over. In oocyte donations, twins reached 27.8% and triplets and over 2.4%. Pre-term births in singletons were 14%. The relative risk of prematurity increased by 4.30 (95% CI 4.1 to 4.6) in twins and 43.8 (95% CI 28.5 to 67.4) in triplets and higher. Perinatal mortality increased from 25.2 per thousand in singletons to 44.4 in twins and 80.7 in triplets and over. Elective single embryo transfer was carried out in only 1.4%, of cycles, with a delivery rate of 30% in women 34 years or younger, and should be considered the way forward provided access is facilitated with public funding.

[Cryopreservation in blastocyst stage effectively reduce the number of embryos cryopreserved]. / La criopreservación embrionaria en estadios más avanzados de desarrollo disminuye la frecuencia de pacientes con embriones criopreservados y el número de embriones criopreservados.

BACKGROUND: Multiple pregnancies are the main complication associated to assisted reproduction, due to the transfer of more than one embryo. Embryo cryopreservation allows the sequential transfer of all generated embryos, thus diminishing the risk of multiple pregnancies. However, it leads to accumulation of cryopreserved embryos. To reduce their accumulation in our unit, we started to preserve embryos as blastocysts, that have a rate of successful pregnancies of approximately 40%. AIM: To perform a sensitivity analysis of this change of policy on the accumulation of embryos. MATERIAL AND METHODS: Records of 571 cycles of in vitro fertilization since 2007 were reviewed, assuming a transference rate of two embryos in women aged less than 35 years and three embryos in older women. The number of embryos that would be preserved as zygotes, eight cell stage or blastocysts, was analyzed. RESULTS: Multiple component logistic regression analysis showed a 20% reduction in the odds ratio of cryopreservation per year of age. There was a 95% reduction in the ratio, when comparing the preservation of third and first day embryos and a 99% reduction when comparing preservation of embryos in blastocyst stage and first day embryos. CONCLUSIONS: Cryopreservation at blastocyst stage effectively decreased the frequency of embryo cryopreservation.

Cost-effectiveness analysis of recombinant human follicle-stimulating hormone alfa(r-hFSH) and urinary highly purified menopausal gonadotropin (hMG) based on data from a large German registry.

This was a retrospective real-world evidence analysis of the costs per live birth for reference recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa) versus highly purified urinary human menopausal gonadotropin (hMG-HP), based on data from a German in vitro fertilization registry (RecDate). Pregnancy and live birth rates from the RecDate real-world evidence study over three complete assisted reproductive technology (ART) cycles using the same gonadotropin drug were used as clinical inputs. Costs related to ART treatment and to drugs were obtained from public sources. Treatment with r-hFSH-alfa resulted in higher adjusted cumulative live birth rates versus hMG-HP after one (25.3% vs. 22.3%), two (30.9% vs. 27.5%), and three (31.9% vs. 28.6%) ART cycles. Costs per live birth were lower with r-hFSH-alfa versus hMG-HP after one (€17,938 vs. €20,054), two (€18,251 vs. €20,437), and three (€18,473 vs. €20,680) ART cycles. r-hFSH-alfa was found to be a cost-effective strategy compared with hMG-HP over three cycles.

Originator recombinant human follitropin alfa versus recombinant human follitropin alfa biosimilars in Spain: A cost-effectiveness analysis of assisted reproductive technology related to fresh embryo transfers.

This study compared the cost per live birth and cost-effectiveness of the originator recombinant human follicle-stimulating hormone follitropin alfa (r-hFSH-alfa) and r-hFSH-alfa biosimilars for ovarian stimulation prior to assisted reproductive technology treatment in Spain. A decision tree model was developed, comprising pregnancy and live birth for one treatment cycle with fresh embryo transfer. Clinical inputs were based on a recent meta-analysis by Chua et al. [4]. Cost inputs were extracted from publicly available Spanish sources. The costs per live birth were lower with originator r-hFSH-alfa (€18,138) versus r-hFSH-alfa biosimilars (€20,377). The incremental cost-effectiveness ratio was €7208 for originator r-hFSH-alfa versus biosimilars. Drug acquisition costs for originator r-hFSH-alfa represented 10.5% of total costs in the base case analysis, and 6.2% in a treatment cycle resulting in live birth with one fresh embryo transfer. Results from the sensitivity analyses confirmed the robustness of the findings.

Atosiban improves the outcome of embryo transfer. A systematic review and meta-analysis of randomized and non-randomized trials.

OBJECTIVE: To estimate the effectiveness of Atosiban in improving the outcome after embryo transfer. The effectiveness of embryo transfer per cycle is still relatively low. One possible explanation might be uterine contractility that expels the transferred embryos. Atosiban improved the outcome of embryo transfer by reducing uterine contractility. METHODS: Data sources: A systematic review of papers in English using MEDLINE and EMBASE (1990-2019). Search terms included Atosiban, embryo transfer. Study selection: We included studies that compared the outcomes of embryo transfer with Atosiban and a control group. Data Extracting: Independent extraction of papers by two authors, using predefined data fields, including study quality indicators. RESULTS: All pooled analyses were based on a fixed-effect model. Four randomised controlled trials, including 1,025 women, and two non-randomised trials, including 686 patients, met our inclusion criteria. In both studies, the heterogeneity was moderate. Atosiban increased clinical pregnancy rates regardless of the indication for ART or type of embryo transferred. Pooled OR in randomized controlled trials reached 1.47 (1.18-1.82), and in non-randomised controlled trials it reached 1.50 (95% CI 1.10-2.05). CONCLUSION: Atosiban appears to increase the clinical pregnancy rates in women undergoing embryo transfer.

Assisted reproductive techniques in Latin America: The Latin American registry, 2016.

RESEARCH QUESTION: What was the utilization, effectiveness and perinatal outcome of assisted reproductive technologies (ART) performed in Latin America during 2016. DESIGN: Retrospective collection of multinational data on ART performed in 178 institutions from 15 Latin American countries. RESULTS: We are reporting 85,474 initiated cycles, 15,070 deliveries and 18,182 babies born in this period. Of all fresh autologous IVF/ICSI cycles, 40.9% were performed in women aged 35-39 years, and 31.1% in women aged ≥40 years. After removing freeze-all cycles, delivery rate per oocyte retrieval was 20.31% for ICSI and 21.85% for IVF. Fresh single embryo transfer including all age categories represented 22.96%, with a 15.35% delivery rate per transfer. Double embryo transfer represented 61.58% of transfers, with a 27.62% delivery rate per transfer. Multiple births included 18.12% twins and 0.55% triplets and higher. In oocyte donation, delivery rate per transfer was 32.89%, with a twin and triplet rate of 23.48% and 0.73%, respectively. Overall, preterm deliveries reached 17.11% in singletons, 65.69% in twins and 95.51% in triplets. Perinatal mortality was 8.0 ‰ in singletons, 19.0 ‰ in twins, and 62.3 ‰ in high-order multiples. CONCLUSIONS: The number of initiated cycles continues to increase. Compared with previous years, the number of embryos transferred decreased while the proportion of single embryo transfers increased with a drop in multiple births. It is mandatory to stimulate health care providers and consumers to continue in this trend.

Assisted Reproductive Techniques in Latin America: The Latin American Registry, 2015.

RESEARCH QUESTION: What was the utilization, effectiveness and safety of assisted reproductive technologies (ART) performed in Latin American countries during 2015, and what were the regional trends? DESIGN: Retrospective collection of multinational data on assisted reproduction techniques (IVF and intracytoplasmic sperm injection [ICSI], frozen embryo transfer, oocyte donation, preimplantation genetic testing and fertility preservation), from 175 institutions in 15 Latin American countries. RESULTS: In total, 41.25% of IVF/ICSI cycles were performed in women aged 35-39 years, and 28.35% in women aged ≥40 years. After removing freeze-all cycles, delivery rate per oocyte retrieval was 21.39% for ICSI and 24.29% for IVF. Multiple births included 19.58% twins and 0.95% triplets and higher. In oocyte donation, delivery rate per transfer was 36.77%, with a twin and triplet rate of 27.65% and 1.06%, respectively. Overall, preterm deliveries reached 17.38% in singletons, 64.94% in twins and 98.41% in triplets. Perinatal mortality in 14,936 births and 18,391 babies born was 10.5 per 1000 in singletons, 17.9 per 1000 in twins, and 57.1 per 1000 in high-order multiples. Elective single embryo transfer represented 3.11% of fresh transfers, with a 31.78% delivery rate per transfer. Elective double embryo transfer represented 23.3% of transfers, with a 37.79% delivery rate per transfer. Out of 18,391 babies born, 63.22% were singletons, 34.4% twins, and 2.38% triplets and higher. CONCLUSIONS: Given the effect of multiple births on prematurity, morbidity and perinatal mortality, reinforcing the existing trend of reducing the number of embryos transferred remains mandatory.

Does acupuncture the day of embryo transfer affect the clinical pregnancy rate? Systematic review and meta-analysis.

The effects of acupuncture on IVF outcomes is still unknown. We carried out a systematic review and meta-analysis of RCT to determine whether acupuncture performed at the time of ET improves outcomes. We searched Medline and Embase from January 1990 to June 2017, for the following terms): (acupuncture; acupuncture therapy) and (reproductive techniques, assisted; in vitro fertilization; embryo transfer). We selected RCT that compared acupuncture with sham acupuncture or no treatment. We included only trials in which acupuncture involved the insertion of needles into traditional meridian points. We evaluated the methodological quality of the trials using the Cochrane risk of bias tool. The measure of treatment effect was the pooled odds ratio of achieving a clinical pregnancy, ongoing pregnancy, or live birth for women in the acupuncture group compared with women in the control group. For pooled data, summary test statistics were calculated using the Mantel-Haenszel method, using the Rev-Man software, version 5.1. We analyzed six studies, including 2,376. In all trials, there were no significant differences between the groups concerning the mean numbers of embryos transferred, the mean age of the women undergoing the procedure, diagnose and use of ICSI. Acupuncture performed the day of ET was associated with a reduced risk of clinical pregnancy (0.87, 95% confidence interval 0.77 to 0.98). The pooled rate difference was -0.06 (-0.12 to -0.01) for clinical pregnancy. None of the trials reported significant adverse effects of acupuncture.

DHEA use to improve likelihood of IVF/ICSI success in patients with diminished ovarian reserve: A systematic review and meta-analysis.

The aim of this review is to determine if the use of DHEA increases the likelihood of success in patients with POR. We searched MEDLINE and EMBASE using the terms "DHEA and diminished ovarian reserve", "DHEA and poor response", "DHEA and premature ovarian aging". A fixed effects model was used and Peto's method to get the odds ratio (OR) with 95% confidence intervals (CI 95%). For quantitative variables, Cohen's method was used to present the standardized mean differences (SMD) with their corresponding confidence intervals. Only five studied fulfilled the selection criteria. DHEA was administered in 25 mg doses, three times a day. In all studies, the authors corrected for the presence of confounding variables such as partner's age, infertility diagnosis and number of transferred embryos. The meta-analysis of the five selected studies assessed a total of 910 patients, who underwent IVF/ICSI, of which 413 had received DHEA. DHEA use was associated with a significant increase in pregnancy likelihood (OR 1.8, CI 95% 1.29 to 2.51, p=0.001). When analyzing the association between DHEA use and the likelihood of abortion, we found low heterogeneity between studies (I2=0.0%) and the use of DHEA to be associated to a significant reduction in the likelihood of abortion (OR 0.25, CI 0.07 to 0.95; p=0.045). Analysis of the association of DHEA with average oocyte retrieval showed high variability between studies (I2=98.6%), as well as no association between DHEA use and the number of oocytes retrieved (SMD -0.01, CI 95% -0.16 to 0.13; p<0.05).