Matheus Roque

Fresh embryo transfer versus frozen embryo transfer in in vitro fertilization cycles: a systematic review and meta-analysis

OBJECTIVE To examine the available evidence to assess if cryopreservation of all embryos and subsequent frozen embryo transfer (FET) results in better outcomes compared with fresh transfer. DESIGN Systematic review and meta-analysis. SETTING Centers for reproductive care. PATIENT(S) Infertility patient(s). INTERVENTION(S) An exhaustive electronic literature search in MEDLINE, EMBASE, and the Cochrane Library was performed through December 2011. We included randomized clinical trials comparing outcomes of IVF cycles between fresh and frozen embryo transfers. MAIN OUTCOME MEASURE(S) The outcomes of interest were ongoing pregnancy rate, clinical pregnancy rate, and miscarriage. RESULT(S) We included three trials accounting for 633 cycles in women aged 27-33 years. Data analysis showed that FET resulted in significantly higher ongoing pregnancy rates and clinical pregnancy rates. CONCLUSION(S) Our results suggest that there is evidence that IVF outcomes may be improved by performing FET compared with fresh embryo transfer. This could be explained by a better embryo-endometrium synchrony achieved with endometrium preparation cycles.

Freeze-all policy: is it time for that?

PurposeThis publication will evaluate the available evidence in the literature comparing fresh embryo transfer (ET) and elective frozen-thawed embryo transfer (FET) regarding the possible interference of controlled ovarian stimulation (COS) in implantation and endometrial receptivity, IVF safety, and obstetric and perinatal outcomes.MethodsWe performed a review in the literature of the available evidence comparing fresh to elective FET (freeze-all policy).ResultsThe improvements made in cryopreservation techniques have led to few or no detrimental effects to the embryo and have resulted in no consequences to the offspring when compared to fresh embryos; this has allowed reproductive practitioners to create the freeze-all policy (when all viable embryos are electively cryopreserved in the fresh cycle and transferred in a posterior cycle). There are increasing concerns about the adverse effects associated with COS over the endometrial and uterine environments, as well as with the safety of COS in pregnancies that have originated from fresh ET during in vitro fertilization (IVF) treatments. COS may contribute to modifications in the endometrium, which might be related to poorer outcomes when fresh ET is performed. It has been suggested that obstetric and perinatal outcomes in pregnancies resulting from fresh ET are poorer when compared with those that occur after FET. In cycles with fresh ET, there is still a risk of ovarian hyperstimulation syndrome (OHSS).ConclusionThere is growing evidence in the literature suggesting better IVF outcomes, and decreased obstetric and perinatal morbidity when adopting the freeze-all policy instead of fresh ET.

Outcome of varicocele repair in men with nonobstructive azoospermia: systematic review and meta-analysis.

The objective of this systemic review was to evaluate the benefit of repairing clinical varicocele in infertile men with nonobstructive azoospermia (NOA). The surgically obtained sperm retrieval rate (SRR) and pregnancy rates following assisted reproductive technology (ART) with the use of retrieved testicular sperm were the primary outcomes. The secondary outcomes included the presence of viable sperm in postoperative ejaculate to avoid the testicular sperm retrieval and pregnancy rates (both assisted and unassisted) using postoperative ejaculated sperm. An electronic search to collect the data was performed using the MEDLINE and EMBASE databases until April 2015. Eighteen studies were included in this systematic review and accounted for 468 patients who were diagnosed with NOA and varicocele. These patients were subjected to either surgical varicocele repair or percutaneous embolization. Three controlled studies evaluating sperm retrieval outcomes indicated that in patients who underwent varicocelectomy, SRR increased compared to those without varicocele repair (OR: 2.65; 95% CI: 1.69-4.14; P< 0.001). Although pregnancy rates with the use of testicular sperm favored the varicocelectomy group, results were not statistically significant (clinical pregnancy rate OR: 2.07; 95% CI: 0.92-4.65; P= 0.08; live birth rate OR: 2.19; 95% CI: 0.99-4.83; P= 0.05). The remaining fifteen studies reported postoperative semen analysis results. In 43.9% of the patients (range: 20.8%-55.0%), sperm were found in postoperative ejaculates. Pregnancy rates for unassisted and assisted (after IVF/ICSI) were 13.6% and 18.9% in the group of men with sperm in postoperative ejaculates, respectively. Our findings indicate that varicocelectomy in patients with NOA and clinical varicocele is associated with improved SRR. In addition, approximately 44% of the treated men will have enough sperm in the ejaculate to avoid sperm retrieval. Limited data on pregnancy outcomes with both postoperative ejaculated sperm and harvested testicular sperm preclude any firm conclusion with regard to the possible increased fertility potential in treated individuals. In conclusion, the results of our study indicate that infertile men with NOA and clinical varicocele benefit from varicocelectomy.  Given the low/moderate quality of evidence available, it is advisable that doctors discuss with their patients with NOA the risks and benefits of varicocele repair.

Outcome of assisted reproductive technology in men with treated and untreated varicocele: systematic review and meta-analysis.

Varicocele affects approximately 35%-40% of men presenting for an infertility evaluation. There is fair evidence indicating that surgical repair of clinical varicocele improves semen parameters, decreases seminal oxidative stress and sperm DNA fragmentation, and increases the chances of natural conception. However, it is unclear whether performing varicocelectomy in men with clinical varicocele prior to assisted reproductive technology (ART) improve treatment outcomes. The objective of this study was to evaluate the role of varicocelectomy on ART pregnancy outcomes in nonazoospermic infertile men with clinical varicocele. An electronic search was performed to collect all evidence that fitted our eligibility criteria using the MEDLINE and EMBASE databases until April 2015. Four retrospective studies were included, all of which involved intracytoplasmic sperm injection (ICSI), and accounted for 870 cycles (438 subjected to ICSI with prior varicocelectomy, and 432 without prior varicocelectomy). There was a significant increase in the clinical pregnancy rates (OR = 1.59, 95% CI: 1.19-2.12, I 2 = 25%) and live birth rates (OR = 2.17, 95% CI: 1.55-3.06, I 2 = 0%) in the varicocelectomy group compared to the group subjected to ICSI without previous varicocelectomy. Our results indicate that performing varicocelectomy in patients with clinical varicocele prior to ICSI is associated with improved pregnancy outcomes.

Letrozole versus clomiphene citrate in polycystic ovary syndrome: systematic review and meta-analysis

Abstract The objective of the present systematic review and meta-analysis was to examine the literature and to identify the results of randomized controlled trials (RCTs) comparing the use of letrozole to clomiphene citrate (CC) for ovulation induction in patients with polycystic ovary syndrome (PCOS). An exhaustive electronic literature search was performed using the MEDLINE and EMBASE databases until October 2014. Seven prospective RCTs comparing the use of letrozole to CC in PCOS patients met the inclusion criteria. Overall, the seven included studies accounted for 1833 patients (906 in the letrozole group and 927 in the CC group) and for 4999 ovulation induction cycles (2455 in the letrozole group and 2544 in the CC group). Five of the included studies reported data on live birth rates. There was a statistically significant increase in the live birth and pregnancy rates in the letrozole group when compared to the CC group, with a relative risk (RR) = 1.55 (95% confidence interval (CI): 1.26–1.90; I2 = 0%) and RR = 1.38 (95% CI: 1.05–1.83; I2 = 61%), respectively. There were no differences in the multiple pregnancy, miscarriage and ovulation rates between the two groups. Our study found that letrozole is superior to CC when considering the live birth and pregnancy rates in patients with PCOS.

Follicular flushing during oocyte retrieval: a systematic review and meta-analysis

PurposeThe purpose of this systematic review and meta-analysis was to examine the literature and identify randomized controlled trials (RCTs), in order to answer if performing follicular flushing during the oocyte retrieval may improve the assisted reproductive technologies (ART) outcomes.MethodsAn exhaustive electronic search was performed using MEDLINE and EMBASE databases. Only RCTs comparing follicular flushing to aspiration only during ART, were included. We included 5 trials, with a total of 482 patients randomized, with median ages ranging from 30.5 to 37.1.ResultsThe data analyses did not show significant differences regarding live birth rate, clinical pregnancies rates, and the number of oocytes retrieved. The duration of oocyte retrieval was significantly increased in the follicular flushing group.ConclusionsThe results from this systematic review and meta-analysis suggest that there is no advantage to use of routine follicular flushing during OR in an unselected group of patients.

A systematic review of clinical practice guidelines and best practice statements for the diagnosis and management of varicocele in children and adolescents.

A systematic review was conducted to identify and qualitatively analyze the methods as well as recommendations of Clinical Practice Guidelines (CPG) and Best Practice Statements (BPS) concerning varicocele in the pediatric and adolescent population. An electronic search was performed with the MEDLINE, EMBASE, Science Direct, and Scielo databases, as well as guidelines′ Web sites until September 2015. Four guidelines were included in the qualitative synthesis. In general, the recommendations provided by the CPG/BPS were consistent despite the existence of some gaps across the studies. The guidelines issued by the American Urological Association (AUA) and American Society for Reproductive Medicine (ASRM) did not provide evidence-based levels for the recommendations given. Most of the recommendations given by the European Association of Urology (EAU) and European Society of Pediatric Urology (ESPU) were derived from nonrandomized clinical trials, retrospective studies, and expert opinion. Among all CPG/BPS, only one was specifically designed for the pediatric population. The studied guidelines did not undertake independent cost-effectiveness and risk-benefit analysis. The main objectives of these guidelines were to translate the best evidence into practice and provide a framework of standardized care while maintaining clinical autonomy and physician judgment. However, the limitations identified in the CPG/BPS for the diagnosis and management of varicocele in children and adolescents indicate ample opportunities for research and future incorporation of higher quality standards in patient care.

Reproductive outcomes of testicular versus ejaculated sperm for intracytoplasmic sperm injection among men with high levels of DNA fragmentation in semen: systematic review and meta-analysis

OBJECTIVE To compare sperm DNA fragmentation (SDF) levels between testicular and ejaculated sperm and to evaluate outcomes of intracytoplasmic sperm injection (ICSI) with the use of testicular (Testi-ICSI) versus ejaculated (Ejac-ICSI) sperm in nonazoospermic men with high SDF. DESIGN Systematic review and meta-analysis. SETTING Not applicable. PATIENT(S) Normo- and oligozoospermic men with high levels of SDF in semen subjected to Testi-ICSI or Ejac-ICSI. INTERVENTION(S) Summary mean difference (MD) and odds ratio (OR) were calculated with the use of an inverse variance model and fixed- or random-effects models, respectively. MAIN OUTCOME MEASURE(S) Primary outcomes were SDF levels, clinical pregnancy rates (CPRs), and live birth rates (LBRs). Secondary outcomes were fertilization and miscarriage rates. RESULT(S) Five studies involving 143 patients provided paired SDF rates for testicular and ejaculated sperm, revealing lower SDF in testicular sperm (MD -24.58%). Four studies involving 507 cycles and 3,840 oocytes reported clinical outcomes of Testi-ICSI and Ejac-ICSI. Fertilization rates were not different between sperm sources, but a trend to lower rates was observed with Testi-ICSI. CPRs were higher for Testi-ICSI than for Ejac-ICSI, as were LBRs, whereas miscarriage rates were reduced with Testi-ICSI. CONCLUSION(S) Testicular sperm have lower levels of SDF than ejaculated sperm, with Testi-ICSI for high post-testicular SDF men improving reproductive outcomes compared with Ejac-ICSI. Infertile couples may benefit from Testi-ICSI if male partners have confirmed high SDF in the ejaculate.

GnRH Agonist Trigger and LH Activity Luteal Phase Support versus hCG Trigger and Conventional Luteal Phase Support in Fresh Embryo Transfer IVF/ICSI Cycles—A Systematic PRISMA Review and Meta-analysis

Introduction The use of GnRH agonist (GnRHa) for final oocyte maturation trigger in oocyte donation and elective frozen embryo transfer cycles is well established due to lower ovarian hyperstimulation syndrome (OHSS) rates as compared to hCG trigger. A recent Cochrane meta-analysis concluded that GnRHa trigger was associated with reduced live birth rates (LBRs) in fresh autologous IVF cycles compared to hCG trigger. However, the evidence is not unequivocal, and recent trials have found encouraging reproductive outcomes among couples undergoing GnRHa trigger and individualized luteal LH activity support. Thus, the aim was to compare GnRHa trigger followed by luteal LH activity support with hCG trigger in IVF patients undergoing fresh embryo transfer. Material and methods We conducted a systematic review and meta-analysis of randomized trials published until December 14, 2016. The population was infertile patients submitted to IVF/ICSI cycles with GnRH antagonist cotreatment who underwent fresh embryo transfer. The intervention was GnRHa trigger followed by LH activity luteal phase support (LPS). The comparator was hCG trigger followed by a standard LPS. The critical outcome measures were LBR and OHSS rate. The secondary outcome measures were number of oocytes retrieved, clinical and ongoing pregnancy rates, and miscarriage rates. Results A total of five studies met the selection criteria comprising a total of 859 patients. The LBR was not significantly different between the GnRHa and hCG trigger groups (OR 0.84, 95% CI 0.62, 1.14). OHSS was reported in a total of 4/413 cases in the GnRHa group compared to 7/413 in the hCG group (OR 0.48, 95% CI 0.15, 1.60). We observed a slight, but non-significant increase in miscarriage rate in the GnRHa triggered group compared to the hCG group (OR 1.85; 95% CI 0.97, 3.54). Conclusion GnRHa trigger with LH activity LPS resulted in comparable LBRs compared to hCG trigger. The most recent trials reported LBRs close to unity indicating that individualization of the LH activity LPS improved the luteal phase deficiency reported in the first GnRHa trigger studies. However, LPS optimization is needed to further limit OHSS in the subgroup of normoresponder patients (<14 follicles ≥ 11 mm). Prospero registration number CRD42016051091

Cost-Effectiveness of the Freeze-All Policy

OBJECTIVE To evaluate the cost-effectiveness of freeze-all cycles when compared to fresh embryo transfer. METHODS This was an observational study with a cost-effectiveness analysis. The analysis consisted of 530 intracytoplasmic sperm injection (ICSI) cycles in a private center in Brazil between January 2012 and December 2013. A total of 530 intracytoplasmic sperm injection (ICSI) cycles - 351 fresh embryo transfers and 179 freeze-all cycles - with a gonadotropin-releasing hormone (GnRH) antagonist protocol and day 3 embryo transfers. RESULTS The pregnancy rate was 31.1% in the fresh group and 39.7% in the freeze-all group. We performed two scenario analyses for costs. In scenario 1, we included those costs associated with the ICSI cycle (monitoring during controlled ovarian stimulation [COS], oocyte retrieval, embryo transfer, IVF laboratory, and medical costs), embryo cryopreservation of supernumerary embryos, hormone measurements during COS and endometrial priming, medication use (during COS, endometrial priming, and luteal phase support), ultrasound scan for frozen- thawed embryo transfer (FET), obstetric ultrasounds, and miscarriage. The total cost (in USD) per pregnancy was statistically lower in the freeze-all cycles (19,156.73 ± 1,732.99) when compared to the fresh cycles (23,059.72 ± 2,347.02). Even in Scenario 2, when charging all of the patients in the freeze-all group for cryopreservation (regardless of supernumerary embryos) and for FET, the fresh cycles had a statistically significant increase in treatment costs per ongoing pregnancy. CONCLUSIONS The results presented in this study suggest that the freeze-all policy is a cost-effective strategy when compared to fresh embryo transfer.