How to optimize culture media osmolality during Assisted Reproductive Technologies treatments.

OBJECTIVE: The objective of our study was to compare the osmolality in sequential and single step culture media, used for in vitro human embryo culture, covered with mineral oil and paraffin, in dry and humid incubators. METHODS: We performed a prospective observational study. A total of 120 Petri dishes, with 960 droplets of culture media, were evaluated. Each dish was prepared with 4 droplets of single step medium and sequential medium. Sixty dishes were covered with mineral oil and 60 with paraffin oil. Half were incubated in a dry incubator and half in a humid. Osmolality was measured on days 1, 3, 5, 7. ANOVA test was performed for statistical analysis. RESULTS: Osmolality results for single step and sequential medium, that were covered with both mineral and paraffin oil and placed in the dry incubator, significantly increased throughout the study time (D7>D5>D3). In the humid incubator, the results were similar for all periods. Osmolality was significantly lower in humid incubator, in all periods, when droplets were covered with both oils. When both culture media were placed in the humid incubator, no variation was detected, using both oils. However, when single step medium was placed in the dry incubator, covered with mineral oil, we observed a higher osmolality than the covered with paraffin oil. CONCLUSIONS: TWe can conclude that humid incubator is better for maintaining osmolality and paraffin oil protect single step media from evaporation in dry incubator.

Growth Hormone Administration to Improve Reproductive Outcomes in Women with Recurrent Implantation Failure (RIF): a Systematic Review.

Recurrent implantation failure (RIF) has been used to describe embryos' failure to implant following IVF, arising concerns about the importance of its treatment. Growth hormone (GH) has been studied as one of the possible co-interventions. Our updated review evaluated GH intervention vs. no intervention from randomized controlled trials (RCTs) in RIF patients. Electronic searches on The Menstrual Disorders and Subfertility Group (MDSG), The Cochrane Central Register for Clinical Trials, PubMed MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS, and Google Scholar up to August 2021 identified 2 RCTs and compiled with the above inclusion criteria. The risk of bias (ROB) and the quality of evidence were assessed according to the Cochrane Collaboration tool and GRADE group guidelines. Meta-analysis found higher rates of clinical pregnancy (OR: 4.97 CI 95% 2.05 to 12.05), live birth (OR: 5.13 CI 95% 2.03 to 12.91), and implantation (OR: 3.88 CI 95% 1.91 to 7.88) when compared GH to no intervention; as well as an increased endometrial thickness (mean difference: 1.14 CI 95% -0.0 to 2.28). However, this review cannot provide a strong recommendation due to the quality of evidence rated as "very low quality of evidence" in all the outcomes for reasons such as methodology issues, heterogeneity, intervention regimen, and limited sample sizes with large confidence intervals and a low number of events. We emphasize the importance of upcoming high-quality research and the need for consensus concepts in RIF patients, which may be a minority; it is still one of the highest impacts on life quality.

Accuracy of Transvaginal Ultrasound in the Diagnosis of Intrauterine Lesions.

OBJECTIVE: To evaluate the accuracy of transvaginal ultrasound in the diagnosis of intrauterine lesions, using hysteroscopy as the gold standard. METHODS: This was a prospective observational study with 307 patients. All patients underwent hysteroscopy after a previous transvaginal ultrasound to compare the results. The hysteroscopy was performed by experienced examiners, and transvaginal ultrasounds were performed in various public and private services, which is reflective of routine healthcare practices in obstetrics and gynecology. The sensitivity, specificity, and accuracy of the transvaginal ultrasound were calculated using hysteroscopy as the gold standard. The level of agreement between the two exams was calculated using the Kappa test. RESULTS: The mean age was 56.55 ± 12.3 years. For endometrial polyps, we observed a sensitivity of 39.8%, specificity of 72.7%, accuracy of 52.8%, and Kappa index of 0.11 (p = 0.025). For fibroids, the sensitivity was 46.7%, specificity was 95.0%, accuracy was 87.9%, and Kappa index was 0.46 (p < 0.001). For endometrial thickening, the sensitivity was 68.7%, specificity was 41.7%, accuracy was 47.6%, and Kappa index was 0.06 (p = 0.126). For endometrial atrophy, we found a sensitivity of 6.7%, specificity of 99.3%, accuracy of 90.2%, and Kappa index of 0.10 (p = 0.006). For the other findings, the sensitivity was 15.6%, specificity was 99.6%, accuracy was 87.3%, and Kappa index was 0.23 (P < 0.001). CONCLUSION: Our study demonstrated a low level of accuracy of transvaginal ultrasound for the diagnosis of endometrial lesions, when performed by a non-experienced professional. Thus, it is important to consider the use of hysteroscopy to avoid unnecessary and inappropriate treatments.

OBJETIVO: Avaliar a acurácia do ultrassom transvaginal para o diagnóstico de lesões intrauterinas, tendo a histeroscopia como padrão de referência. MéTODOS: Foi realizado um estudo observacional prospectivo em 307 pacientes, submetidas à histeroscopia após ultrassonografia prévia para comparação dos resultados. A histeroscopia foi realizada por duas médicas com experiência, e os exames de ultrassom foram realizados em diversas fontes, públicas ou privadas, como ocorre no cotidiano da assistência à saúde em nosso meio. Foram avaliados sensibilidade, especificidade e acurácia, tendo a histeroscopia como padrão-ouro. O nível de concordância foi avaliado pelo teste de Kappa. RESULTADOS: A idade média foi de 56,55 ± 12,3 anos. Os resultados para pólipo endometrial foram: sensibilidade 39.8%, especificidade 72,7%, acurácia de 52,8%, e índice Kappa 0,11 (p = 0,025). Para mioma, sensibilidade 46,7%, especificidade 95,0%, acurácia 87,9%, e índice Kappa 0,46 (p < 0,001). Para espessamento endometrial, sensibilidade 68,7%, especificidade 41,7%, acurácia 47,6%, e índice Kappa de 0,06 (p = 0,126). Para atrofia, sensibilidade 6,7%, especificidade 99,3%, acurácia 90,2%, e índice Kappa 0,10 (p = 0,006). Para outros achados, sensibilidade 15,6%, especificidade 99,6%, acurácia 87,3%, e índice Kappa 0,23 (p < 0,001). CONCLUSãO: Nosso estudo demonstrou baixo nível de acurácia da ultrassonografia transvaginal para o diagnóstico de lesões endometriais, quando realizada por profissional não experiente. Assim, é importante considerar o uso da histeroscopia para evitar tratamentos desnecessários e inadequados.

Ultrastructural analysis of Lyophilized Human Spermatozoa.

OBJECTIVE: Lyophilization is potentially more practical and cost-effective alternative for sperm preservation. However, there are no studies that evaluate the ultrastructure of human spermatozoa after lyophilization. Therefore, the aim of our study was to evaluate the ultrasctructure of lyophilized spermatozoa using Transmission Electron Microscopy. METHODS: From a total of 21 donated seminal samples, 30 aliquots were originated and divided into two aliquots so that one could have been submitted to cryopreservation/thaw and the other for lyophilization/rehydration. The liquefied aliquots were homogenized at room temperature. Samples assigned for cryopreservation were placed in straws and samples assigned for lyophilization were placed in the appropriate vials. Cryopreservation samples were placed at -30oC for 30 minutes subsequently for 30 minutes at vapour phase and then plunged into liquid nitrogen. Lately, were warmed in water bath at 37oC for 10 minutes followed by 10 minutes centrifugation. The pellet was resuspended and analysed in a Makler chamber. The semen vials assigned for lyophilization were loaded into a pre-fixed freeze-drying chamber. Following lyophilization, vials were removed from the freeze-drying chamber and kept at 4oC until rehydration. TEM was performed after rehydration and thawing. Sperm samples were fixed, rinsed in buffer, post fixed and dehydration was carried out in escalating concentrations of alcohol solution, acetone and then, embedding in Epon resin. Ultrathin sections were stained and examined in a Transmission Electron Microscope. RESULTS: Analysis of sperm after freezing/thawing using Transmission Electron Microscopy showed lesions to the midpiece, with some mitochondria degeneration and random rupture of plasma membrane. In the head, we identified intact plasma membrane, nucleus and acrosome, as in the flagellum all main structures remained intact including the plasma membrane, the longitudinal columns of dense fibers and the semicircular fibers. Analysis by Transmission Electron Microscopy showed that spermatozoa heads had ruptured plasma membranes, absence of acrosomes, nuclei with heterogeneous and decompressed chromatin. Mitochondria were deteriorated in the midpiece. Longitudinal columns of dense fibers were absent in the flagellum. Axonemes, in cross-sections, were disrupted with disorganized structures. CONCLUSIONS: To our knowledge, our study demonstrated, for the first time, the structure of the human spermatozoa after lyophilization using Transmission Electron Microscopy. The use of a fixed lyophilization protocol with media containing cryoprotectants might explain the damage to the structures. More studies are necessary to improve the results of sperm lyophilization. In the future, the use of lyophilization of spermatozoa might reduce the costs of fertility preservation, since there will be no need for storage space and transportation is simpler.

Accuracy of Transvaginal Ultrasound in the Diagnosis of Intrauterine Lesions / Acurácia da ultrasonografia tranvaginal no diagnóstico de lesões intrauterinas

Abstract Objective To evaluate the accuracy of transvaginal ultrasound in the diagnosis of intrauterine lesions, using hysteroscopy as the gold standard. Methods This was a prospective observational study with 307 patients. All patients underwent hysteroscopy after a previous transvaginal ultrasound to compare the results. The hysteroscopy was performed by experienced examiners, and transvaginal ultrasounds were performed in various public and private services, which is reflective of routine healthcare practices in obstetrics and gynecology. The sensitivity, specificity, and accuracy of the transvaginal ultrasound were calculated using hysteroscopy as the gold standard. The level of agreement between the two exams was calculated using the Kappa test. Results Themean age was 56.55±12.3 years. For endometrial polyps, we observed a sensitivity of 39.8%, specificity of 72.7%, accuracy of 52.8%, and Kappa index of 0.11 (p=0.025). For fibroids, the sensitivity was 46.7%, specificity was 95.0%, accuracy was 87.9%, and Kappa index was 0.46 (p<0.001). For endometrial thickening, the sensitivity was 68.7%, specificity was 41.7%, accuracy was 47.6%, and Kappa index was 0.06 (p=0.126). For endometrial atrophy, we found a sensitivity of 6.7%, specificity of 99.3%, accuracy of 90.2%, and Kappa index of 0.10 (p=0.006). For the other findings, the sensitivity was 15.6%, specificity was 99.6%, accuracy was 87.3%, and Kappa index was 0.23 (P<0.001). Conclusion Our study demonstrated a low level of accuracy of transvaginal ultrasound for the diagnosis of endometrial lesions, when performed by a non-experienced professional. Thus, it is important to consider the use of hysteroscopy to avoid unnecessary and inappropriate treatments.

Resumo Objetivo Avaliar a acurácia do ultrassom transvaginal para o diagnóstico de lesões intrauterinas, tendo a histeroscopia como padrão de referência. Métodos Foi realizado um estudo observacional prospectivo em 307 pacientes, submetidas à histeroscopia após ultrassonografia prévia para comparação dos resultados. A histeroscopia foi realizada por duas médicas com experiência, e os exames de ultrassom foram realizados em diversas fontes, públicas ou privadas, como ocorre no cotidiano da assistência à saúde em nosso meio. Foram avaliados sensibilidade, especificidade e acurácia, tendo a histeroscopia como padrão-ouro. O nível de concordância foi avaliado pelo teste de Kappa. Resultados A idade média foi de 56,55±12,3 anos. Os resultados para pólipo endometrial foram: sensibilidade 39.8%, especificidade 72,7%, acurácia de 52,8%, e índice Kappa 0,11 (p=0,025). Para mioma, sensibilidade 46,7%, especificidade 95,0%, acurácia 87,9%, e índice Kappa 0,46 (p<0,001). Para espessamento endometrial, sensibilidade 68,7%, especificidade 41,7%, acurácia 47,6%, e índice Kappa de 0,06 (p=0,126). Para atrofia, sensibilidade 6,7%, especificidade 99,3%, acurácia 90,2%, e índice Kappa 0,10 (p=0,006). Para outros achados, sensibilidade 15,6%, especificidade 99,6%, acurácia 87,3%, e índice Kappa 0,23 (p<0,001). Conclusão Nosso estudo demonstrou baixo nível de acurácia da ultrassonografia transvaginal para o diagnóstico de lesões endometriais, quando realizada por profissional não experiente. Assim, é importante considerar o uso da histeroscopia para evitar tratamentos desnecessários e inadequados.

Effect of Tribulus Terrestris in the Treatment of Female Sexual Dysfunction and Clitoral Vascularization. Results of a Randomized Study Comparing Two Different Dosage Regimes.

We evaluated the efficacy of Tribulus terrestris in two different dosage regimes for the treatment of sexual dysfunction in pre and postmenopausal women and its effect on the vascular resistance of the clitoral artery using Power Doppler. A total of 104 women were randomly assigned to receive 94mg, three times/day (TT3) or 280mg once/day for 90 days (TT1). Evaluation was performed using FSFI and QS-F questionnaires, serum levels of prolactin, TSH, total testosterone and SHBG, and clitoral artery assessment with Power Doppler ultrasound. FSFI results demonstrated an improvement in all domains in both groups (P < 0.05) except for the "Satisfaction" in the TT3 premenopausal group. QS-F results showed a significant improvement in the mean total score in women of both reproductive phases, for both groups. Postmenopausal patients improved in all sexual domains, except for "orgasm" in the TT1 group. PI of the clitoral artery showed no difference in both reproductive phases, in both groups. We conclude that TTerrestris can be a safe alternative for the treatment of sexual dysfunction in pre and postmenopausal women as it is effective in reducing the symptoms with no side effects. Moreover, its use, increased total, free and bioavailable testosterone.

Four consecutive minimal ovarian stimulation (TetraStim) is a feasible alternative to increase the number of oocytes and improve live birth rates in poor responders who do not accept oocyte donation.

OBJECTIVE: To present our experience using four consecutive minimal COS (TetraStim) followed by oocyte retrieval and vitrification to increase the number of oocytes in patients with POR for whom oocyte donation is not an option. METHODS: We performed an observational study evaluating 128 poor responders submitted to TetraStim instead of oocyte donation cycles. Patients were submitted to four consecutive minimal COS started at luteal phase, oocyte retrieval, oocyte vitrification/warming, ICSI, endometrial priming and embryo transfer. We evaluated the number of vitrified oocytes, survival rate after warming, fertilization rate, cleavage rate, number of embryos transferred, clinical pregnancy rate, miscarriage rate and live birth rate. RESULTS: The mean age was 38.1 ± 3.1 years. A total of 791 oocytes were recovered (6.1 ± 2.7/patient), 682 (86.2%) Metaphase II (5.3 ± 2.4/patient) were vitrified, 95.3% survived warming (5.1 ± 2.3/patient), 82% showed normal fertilization after ICSI (4.2 ± 2/patient), 79.2% reached cleavage stage (3.3 ± 1.6/patient), 313 cleavage stage embryos were transferred to 115 patients (2.7 ± 0.7/patient) and 14.7% of the patients had surplus embryos that were vitrified. Clinical pregnancy rate per patient was 31.3% and live birth rate per patient was 22.6%. CONCLUSION: To our knowledge this is the first study that demonstrates that TetraStim can be an effective alternative for patients with POR with an indication to perform IVF with donated oocytes, but do not agree to use. TetraStim is a feasible alternative to increase the number of oocytes and embryos and improve pregnancy rates with no dropouts and very low cycle cancelation rate. However, randomized controlled studies must be performed to compare TetraStim with other treatments.

Do different culture intervals (2 × 24 hours) after thaw of cleavage stage embryos affect pregnancy rates? A randomized controlled trial.

The aim of the study was to evaluate whether selecting embryos for transfer after prolonged culture after thaw (18-24 h) has better pregnancy rates than selecting embryos for transfer after short culture after thaw (2-5 h). We performed a double-blinded, randomized, controlled trial, evaluating 388 patients submitted to ART treatment who had embryos frozen on day-2 and subsequently transferred. All patients received the same endometrial priming with estradiol valerate followed by vaginal progesterone. Patients were randomized for Frozen embryo transfer 2-5 h after thaw (Group D2) or 18-24 h after thaw (Group D2/D3). The main Outcome Measure was ongoing pregnancy rate (OPR) at 20 weeks' gestation per embryo transfer. A total of 179 patients had embryos transferred 2-5 h after thaw and 209 patients had embryos transferred 18-24 h after thaw. The mean age in group D2 was 36 ± 4.4 and 36 ± 5.4 in group D2/D3. Ongoing pregnancy rate was 28% and 33.5% (p = 0.2) for groups D2 and D2/D3, respectively. These results suggest that increasing the culture time of embryos in one day to improve selection before transfer does not increase ongoing pregnancy rate. CLINICAL TRIAL REGISTRATION NUMBER: NCT03381001.

Prevalence of human papillomavirus (HPV) in the semen of patients submitted to assisted reproductive technology treatment in a private clinic in Brazil.

OBJECTIVE: The aim of our study was to identify the prevalence of HPV in the semen of men submitted to ART treatment and look into the possible impacts of the virus on sperm parameters. METHODS: Thirty-five patients treated for infertility from March to August 2016 were invited to join the study. Samples with a minimum concentration of 40x106 spermatozoa per milliliter were included in the study. After the evaluation of semen parameters, DNA extraction and PCR were performed to verify the presence of HPV by electrophoresis in 8% polyacrylamide gel. RESULTS: Patient age ranged from 27 to 68 years (mean 39.2 years). Semen analysis showed a mean volume of 2.5mL; mean concentration of 58.9x106; and mean motility of 51.8%. HPV DNA was identified in seven semen samples from 25 patients (28%). Ten samples with DNA concentrations below 10ng/µL were excluded from the study due to poor amplification quality. There was no statistical difference in sperm concentration when HPV-negative and HPV-positive samples were compared (65.9x106 vs. 62.3x106; p=0.70). However, sperm motility was significantly higher in HPV-positive semen (65% vs. 46.6%; p=0.02). CONCLUSIONS: HPV prevalence was 28% in the semen of patients submitted to ART treatment. HPV-positive samples had statistically increased motility compared to negative samples (65% vs. 46.6%; p=0.02).

Efficacy and safety of a non-hormonal intravaginal moisturizer for the treatment of vaginal dryness in postmenopausal women with sexual dysfunction.

OBJECTIVE: Evaluate the efficacy and safety of a non-hormonal intravaginal moisturizer on reducing the symptoms arising from vaginal dryness and sexual dysfunction. STUDY DESIGN: A total of 37 postmenopausal women used a non-hormonal intravaginal Moisturizer (polycarbophil, butyl ester of a copolymer of methyl vinyl ether/ copolymer PVM/MA, 50% sodium lactate solution, and Carbopol) twice a week for 12 weeks. The vaginal moisture levels, volume of fluid, elasticity, and epithelium integrity were assessed using the Vaginal Health Index. Sexual function was measured using the Female Sexual Function Index questionnaire. All women were evaluated before starting treatment and at the 4th, 8th and 12th weeks of the study. At the end of the study, the patients analysed the treatment regarding to their satisfaction with the product, and its application system, their sense of well-being after using it as well as their perception bout the discharge of the moisturizer (if it run or was held by the vaginal mucosa). RESULTS: There was a significant improvement in the vaginal moisture, fluid volume, elasticity and epithelial integrity (p < 0.001). Sexual function improved in the total score and in all six domains (p < 0.001). More than 50% of all patients reported being very satisfied with the treatment and product application. The sense of well-being was considered very good by 51.4% of the participants and most (91.9%) indicated that the product did not leak and did not stick to the vaginal mucosa. No severe adverse events were reported. CONCLUSION: Our study suggests that treatment with the non-hormonal intravaginal moisturizer is a safe and efficient therapeutic option for the improvement of vaginal dryness with encouraging benefits for the sexual function of postmenopausal women.

Pharmacogenetic algorithm for individualized controlled ovarian stimulation in assisted reproductive technology cycles.

Controlled ovarian stimulation (COS) is crucial for optimizing in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) success. Multiple factors influence the ovarian response to COS, making predictions about oocyte yields not so straightforward. As a result, the ovarian response may be poor or suboptimal, or even excessive, all of which have negative consequences for the affected patient. There is a group of patients that present with a suboptimal response to COS despite normal biomarkers of ovarian reserve, such as AFC and AMH. These patients have a lower number of retrieved oocytes than what was expected based on their ovarian reserve, thus showing the inadequacy of using only the traditional ovarian reserve biomarkers to predict the ovarian response. Suboptimal response to COS might be related to ovarian sensitivity to exogenous gonadotropins modulated by genetic factors. The understanding of the gene polymorphisms related to reproductive function can help to improve the clinical management of this patient population and to explain some of the individual patient variability in response to COS. The development of a pharmacogenetic approach concerning COS in the context of assisted reproduction seems attractive as it might help to understand the relationship between genetic variants and ovarian response to exogenous gonadotropins. The patient's genetic profile could be used to select the most appropriate gonadotropin type, predict the optimal dosage for each drug, develop a cost-effective treatment plan, maximize the success rates, and lastly, decrease the time-to-pregnancy.

Fresh versus elective frozen embryo transfer in IVF/ICSI cycles: a systematic review and meta-analysis of reproductive outcomes.

BACKGROUND: Elective freezing of all good quality embryos and transfer in subsequent cycles, i.e. elective frozen embryo transfer (eFET), has recently increased significantly with the introduction of the GnRH agonist trigger protocol and improvements in cryo-techniques. The ongoing discussion focuses on whether eFET should be offered to the overall IVF population or only to specific subsets of patients. Until recently, the clinical usage of eFET was supported by only a few randomized controlled trials (RCT) and meta-analyses, suggesting that the eFET not only reduced ovarian hyperstimulation syndrome (OHSS), but also improved reproductive outcomes. However, the evidence is not unequivocal, and recent RCTs challenge the use of eFET for the general IVF population. OBJECTIVE AND RATIONALE: This systematic review and meta-analysis aimed at evaluating whether eFET is advantageous for reproductive, obstetric and perinatal outcomes compared with fresh embryo transfer in IVF/ICSI cycles. Additionally, we evaluated the effectiveness of eFET in comparison to fresh embryo transfer in different subgroups of patients undergoing IVF/ICSI cycles. SEARCH METHODS: We conducted a systematic review, using PubMed/Medline and EMBASE to identify all relevant RCTs published until March 2018. The participants included infertile couples undergoing IVF/ICSI with or without preimplantation genetic testing for aneuploidy (PGT-A). The primary outcome was the live birth rate (LBR), whereas secondary outcomes were cumulative LBR, implantation rate, miscarriage, OHSS, ectopic pregnancy, preterm birth, pregnancy-induced hypertension, pre-eclampsia, mean birthweight and congenital anomalies. Subgroup analyses included normal and hyper-responder patients, embryo developmental stage on the day of embryo transfer, freezing method and the route of progesterone administration for luteal phase support in eFET cycles. OUTCOMES: Eleven studies, including 5379 patients, fulfilling the inclusion criteria were subjected to qualitative and quantitative analysis. A significant increase in LBR was noted with eFET compared with fresh embryo transfer in the overall IVF/ICSI population [risk ratio (RR) = 1.12; 95% CI: 1.01-1.24]. Subgroup analyses indicated higher LBRs by eFET than by fresh embryo transfer in hyper-responders (RR = 1.16; 95% CI: 1.05-1.28) and in PGT-A cycles (RR = 1.55; 95% CI: 1.14-2.10). However, no differences were observed for LBR in normo-responders (RR = 1.03; 95% CI: 0.91-1.17); moreover, the cumulative LBR was not significantly different in the overall population (RR = 1.04; 95% CI: 0.97-1.11). Regarding safety, the risk of moderate/severe OHSS was significantly lower with eFET than with fresh embryo transfer (RR = 0.42; 95% CI: 0.19-0.96). In contrast, the risk of pre-eclampsia increased with eFET (RR = 1.79; 95% CI: 1.03-3.09). No statistical differences were noted in the remaining secondary outcomes. WIDER IMPLICATIONS: Although the use of eFET has steadily increased in recent years, a significant increase in LBR with eFET was solely noted in hyper-responders and in patients undergoing PGT-A. Concerning safety, eFET significantly decreases the risk of moderate and severe OHSS, albeit at the expense of an increased risk of pre-eclampsia.

Freeze-all strategy in IVF/ICSI cycles: an update on clinical utility.

Over the years concerns have arisen about possible adverse effects associated with controlled ovarian stimulation (COS) as regards not only the endometrium, but also on obstetrical and perinatal outcomes in pregnancies after fresh embryo transfer (ET) during in-vitro fertilization (IVF) treatment. The improvements in cryopreservation techniques associated with the possible impairment in endometrial receptivity due to the supra-physiologic hormonal levels observed during conventional COS have increased the implementation of the so-called "freeze-all" policy. With this strategy, the entire cohort of embryos is cryopreserved to be transferred to the uterus in subsequent cycles in a more physiological environment, avoiding the supra-physiologic hormonal levels observed during COS. The initial studies showed that this strategy could be beneficial for subgroups of patients, however, the freeze-all policy is being more and more frequently used for all patient categories. Unfortunately, currently, no clinical data support this widespread use of the freeze-all strategy. Based on available trials, it seems justified to implement the strategy in patients with risk of ovarian hyperstimulation syndrome, hyper-responders and when performing preimplantation genetic testing for aneuploidy in blastocyst stage. Therefore, all the other indications, such as implantation failure, high progesterone levels on the trigger day, advanced maternal age, and endometriosis, still lack the evidence to support routine use of the freeze-all policy.

Ovarian response after random-start controlled ovarian stimulation to cryopreserve oocytes in cancer patients.

OBJECTIVE: To evaluate COS and oocyte retrieval results in ART treatment cycles initiated at any stage of the menstrual cycle (random start) in cancer patients, who could not postpone the onset of cancer treatment. METHODS: Prospective observational study of 26 women with cancer, with an indication to start cancer treatment within the next 20 days and wishing to preserve their fertility. Ovarian stimulation started immediately with FSH followed by GnRH antagonist for pituitary suppression and GnRH agonist for oocyte maturation. Treatment started from day 1 to day 14 of the menstrual cycle was considered to be in the follicular phase, and that started from day 15 to day 28 was considered to be in the luteal phase. Oocyte retrieval was performed 34 h after GnRH agonist administration. After identification and maturity classification, metaphase II oocytes were cryopreserved using vitrification. RESULTS: A total of 13 women had breast cancer, 4 ovarian cancer, 3 Central Nervous System cancer, 3 endometrial cancer, 2 cervical cancer and one bowel cancer. Thirteen patients started treatment during follicular phase and 13 during luteal phase. We found similar results for the duration of treatment, total dose of follicle stimulating hormone, number of ampoules of gonadotropin releasing hormone antagonist, mean number of follicles identified at ultrasound on the day of trigger and retrieval, number of aspirated oocytes and Metaphase II oocytes. CONCLUSION: Random-start controlled ovarian stimulation for emergency fertility preservation for minimizing delay in oncologic treatment for cancer patients does not interfere with the number of metaphase II oocytes, and therefore can be routinely used for stimulation followed by cryopreservation.

Endometriosis does not affect live birth rates of patients submitted to assisted reproduction techniques: analysis of the Latin American Network Registry database from 1995 to 2011.

PURPOSE: The purpose of this study is to compare the results of ART treatment in patients with and without endometriosis in a large cohort of patients from different centers over an extented period of time. METHODS: This retrospective study is using data from patients undergoing 27,294 cycles of IVF/ICSI treatment between 1995 and 2011 that were registered in the database of the Latin American Registry maintained by the Latin America Network of Assisted Reproduction. RESULTS: The mean number of retrieved oocytes was higher in the control group, but the mean number of metaphase II oocytes was similar. Fertilization rate and transfer rate were higher in the control group. We observed higher pregnancy rates, per cycle initiated and per embryo transfer and higher live birth rate in the endometriosis group. In the group of patients with 25-35 years old, the number of oocytes, fertilization rate, and number of transferred embryos were significantly higher in the control group. However, pregnancy rate and live birth rate were higher in the endometriosis group. In the group of patients with 36-40 years old, the number of transferred embryos was higher in the control group, but the pregnancy rate and live birth rate were higher in the endometriosis group. In the group of patients with 41 to 42 years old, the number of transferred embryos and the transfer rate were higher in the control group, but the pregnancy rate was higher in the endometriosis group. CONCLUSION: Our results demonstrate that endometriosis does not affect the outcome of patients subjected to IVF/ICSI and although patients with endometriosis present lower number of oocytes and higher cancelation rate, these shortcomings do not reduce pregnancy and live birth rates.

Obstetric outcomes after fresh versus frozen-thawed embryo transfers: A systematic review and meta-analysis.

OBJECTIVE: To evaluate if there are differences in the risks of obstetric outcomes in IVF/ICSI singleton pregnancies when compared fresh to frozen-thawed embryo transfers (FET). METHODS: This was a systematic review and meta-analysis evaluating the obstetric outcomes in singleton pregnancies after FET and fresh embryo transfer. The outcomes included in this study were pregnancy-induced hypertension (PIH), pre-eclampsia, placenta previa, and placenta accreta. RESULTS: The search yielded 654 papers, 6 of which met the inclusion criteria and reported on obstetric outcomes. When comparing pregnancies that arose from FET or fresh embryo transfer, there was an increase in the risk of obstetric complications in pregnancies resulting from FET when compared to those emerging from fresh embryo transfers in PIH (aOR 1.82; 95% CI 1.24-2.68), pre-eclampsia (aOR 1.32, 95% CI 1.07, 1.63), and placenta accreta (aOR 3.51, 95% CI 2.04-6.05). There were no significant differences in the risk between the FET and fresh embryo transfer groups when evaluating placenta previa (aOR 0.70; 95% CI 0.46-1.08). CONCLUSION: The obstetric outcomes observed in pregnancies arising from ART may differ among fresh and FET cycles. Thus, when evaluating to perform a fresh embryo transfer or a freeze-all cycle, these differences found in obstetric outcomes between fresh and FET should be taken into account. The adverse obstetric outcomes after FET found in this study emphasize that the freeze-all policy should not be offered to all the patients, but should be offered to those with a clear indication of the benefit of this strategy.

Efficacy of Tribulus Terrestris for the treatment of premenopausal women with hypoactive sexual desire disorder: a randomized double-blinded, placebo-controlled trial.

Although hypoactive sexual desire disorder (HSDD) is the most common sexual complaint, there is no consensus for the ideal treatment. Our study aimed to evaluate the efficacy of treating premenopausal women with HSDD with Tribulus terrestris and its effect on the serum levels of testosterone. We performed a prospective, randomized, double-blind, placebo-controlled trial, with 40 premenopausal women reporting diminished libido, receiving T. terrestris or placebo. The questionnaires FSFI and the QS-F were used to evaluate sexual dysfunction before and after treatment. Patients treated with T. terrestris experienced improvement in total score of FSFI (p < .001) and domains "desire" (p < .001), "sexual arousal" (p = .005), "lubrication" (p = .001), "orgasm" (p <.001), "pain" (p = .030) and "satisfaction" (p = .001). Treatment with placebo did not improve the scores for the "lubrication" and "pain". QS-F scores showed that patients using T. terrestris had improvements in "desire" (p = .012), "sexual arousal/lubrication" (p = .002), "pain" (p = .031), "orgasm" (p = .004) and "satisfaction" (p = .001). Women treated with placebo did not score improvements. Women receiving T. terrestris had increased levels of free (p = .046) and bioavailable (p < .048) testosterone. T. terrestris might be a safe alternative for the treatment of premenopausal women with HSDD as it was effective in reducing the symptoms, probably due to an increase in the serum levels of free and bioavailable testosterone.

Effect of follicular flushing on reproductive outcomes in patients with poor ovarian response undergoing assisted reproductive technology.

PURPOSE: The purpose of this study is to investigate the impact of follicular flushing on the number of oocytes retrieved, oocyte maturity, fertilization rate, embryo development, and pregnancy rate of poor ovarian responders (POR). METHODS: Retrospective study of 524 cycles of 384 patients with POR submitted to assisted reproductive technology (ART) and who had follicular flushing during oocyte retrieval was used in the study. We included patients with <5 oocytes at oocyte retrieval (POR group) and matching the Bologna criteria. RESULTS: POR patients had a mean age of 38.2 ± 4.2 years. A total of 1355 follicles (mean = 3.5 ± 1.6) were aspirated and 1040 oocytes recovered, with 709 (68.2%) obtained by direct aspiration and 331 (31.8%) by follicular flushing. We found a difference between the total number of oocytes and the number of aspirated oocytes. Overall pregnancy rate was 22%. Association was observed between pregnancy rate and the number of oocytes retrieved, the number of MII oocytes, and the number of embryos transferred. The patients matching the Bologna criteria had a mean age of 38.9 ± 3.9 years. A total of 309 follicles were aspirated (mean = 3.1 ± 1.5) and 242 oocytes recovered, with 156 (64.5%) obtained by direct aspiration and 86 (35.5%) by follicular flushing. There was a significant difference between the total number of oocytes and the number of aspirated oocytes. Overall pregnancy rate was 12.1%. There was no association between the pregnancy rate and the number of oocytes retrieved, the number of MII, and the number of embryos. CONCLUSIONS: Follicular flushing might be a suitable alternative to increase the number of oocytes and pregnancy rates in patients with POR.