Pre- and post-surgical evaluation of the impact on Hansen disease sequealae patients' quality of life submitted to orthopedic surgery for closure of chronic plantar ulcers.

INTRODUCTION: Leprosy is a chronic infectious disease that still persists as a public health problem in Brazil. Plantar ulcers are serious complications due to leprosy neuropathy and intensify the isolation and stigma of these individuals. The difficulty in closing these lesions associated with the fetid odor negatively impact the quality of life of people with these lesions. OBJECTIVE: To evaluate the clinical, socioeconomic conditions, degree of satisfaction and quality of life (QoL) of patients after healing of chronic ulcers on feet submitted to orthopedic surgery. METHODOLOGY: This is a qualitative, exploratory, descriptive and observational study carried out with 92 people after surgical treatment of chronic leprosy plantar ulcers. These patients were submitted to a semi-structured questionnaire raising questions of an epidemiological, socioeconomic and perception of quality-of-life order, comparing before and after the surgical procedure. RESULTS: Decrease in indicators - alcohol consumption, tobacco consumption, average monthly cost of analgesic medications, fetid wound odor, foot pain and number of dressings performed weekly; Recurrence of lesions in 55.4 % of cases, related to irregular use or lack of shoes and insoles; Improvement in self-perception of Quality of Life (QoL) in 89.1 % of patients after surgery. CONCLUSION: Orthopedic surgical treatment with resection of plantar bony prominences and skin grafting is an effective therapeutic method for closing chronic plantar ulcers in leprosy, resulting in a decrease in the financial costs employed and in an important improvement in the Quality-of-Life parameters of the individuals undergoing to this procedure. The availability and regular use of shoes and insoles is crucial to prevent recurrence of these injuries.

Comparing Two- and Three-dimensional Antral Follicle Count in Patients with Endometriosis.

Background: The purpose of the study was to compare three-dimensional (3D) ultrasound semiautomatic antral follicle count (AFC) with two-dimensional (2D) ultrasound real-time AFC to evaluate patients with deep endometriosis and/or endometrioma submitted to ovarian stimulation (OS). Methods: This was a retrospective cohort study assessing all women with documented diagnosis of deep endometriosis who underwent OS for assisted reproduction treatment. The primary outcome was the difference between AFC by semiautomatic 3D follicle count using 3D volume datasets and 2D ultrasound count with the number of oocytes retrieved at the end of the cycle. The 3D ultrasound AFC was obtained using sonography-based automated volume count (SonoAVC), and the 2D ultrasound AFC data was collected from the electronic medical record. Results: Total of 36 women had deep endometriosis documented by magnetic resonance imaging, laparoscopy, or ultrasonography and 3D ovarian volume datasets stored from their first exam. The differences between the 2D and 3D AFC and the number of oocytes retrieved at the end of the stimulation were compared, showing no significant statistical difference between both methods (P = 0.59). Correlations were similar using both methods when compared to the number of oocytes retrieved (2D [r = 0.83, confidence interval (CI) = 0.68-0.9, P < 0.001]); (3D [r = 0.81, CI = 0.46-0.83, P < 0.001]). Conclusion: 3D semiautomatic AFC can be used to access the ovarian reserve in patients with endometriosis.

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.

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.

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.

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.

Freeze-all cycle in reproductive medicine: current perspectives.

The freeze-all strategy has emerged as an alternative to fresh embryo transfer (ET) during in vitro fertilization (IVF) cycles. Although fresh ET is the norm during assisted reproductive therapies (ART), there are many concerns about the possible adverse effects of controlled ovarian stimulation (COS) over the endometrium. The supra-physiologic hormonal levels that occur during a conventional COS are associated with modifications in the peri-implantation endometrium, which may be related to a decrease in pregnancy rates and poorer obstetric and perinatal outcomes when comparing fresh to frozen-thawed embryo transfers. The main objective of this study was to assess the available literature regarding the freeze-all strategy in IVF cycles, in regards to effectiveness and safety. Although there are many potential advantages in performing a freeze-all cycle over a fresh ET, it seems that the freeze-all strategy is not designed for all IVF patients. There is a need to develop a non-invasive clinical tool to evaluate the endometrial receptivity during a fresh cycle, which enables the selection of patients that would benefit from this strategy. Today, it is reasonable to perform elective cryopreservation of all oocytes/embryos in cases with a risk of OHSS development, and in patients with supra-physiologic hormonal levels during the follicular phase of COS. It is not clear if all normal responders and poor responders may benefit from this strategy.

Freeze-all cycle for all normal responders?

PURPOSE: The purpose of this study is to evaluate the freeze-all strategy in subgroups of normal responders, to assess whether this strategy is beneficial regardless of ovarian response, and to evaluate the possibility of implementing an individualized embryo transfer (iET) based on ovarian response. METHODS: This was an observational, cohort study performed in a private IVF center. A total of 938 IVF cycles were included in this study. The patients were submitted to controlled ovarian stimulation (COS) with a gonadotropin-releasing hormone (GnRH) antagonist protocol and a cleavage-stage day 3 embryo transfer. We performed a comparison of outcomes between the fresh embryo transfer (n = 523) and the freeze-all cycles (n = 415). The analysis was performed in two subgroups of patients based on the number of retrieved oocytes: Group 1 (4-9 oocytes) and Group 2 (10-15 oocytes). RESULT(S): In Group 1 (4-9 retrieved oocytes), the implantation rates (IR) were 17.9 and 20.5% (P = 0.259) in the fresh and freeze-all group, respectively; the ongoing pregnancy rates (OPR) were 31 and 33% (P = 0.577) in the fresh and freeze-all group, respectively. In Group 2 (10-15 oocytes), the IR were 22.1 and 30.1% (P = 0.028) and the OPR were 34 and 47% (P = 0.021) in the fresh and freeze-all groups, respectively. CONCLUSION(S): Although the freeze-all policy may be related to better in vitro fertilization (IVF) outcomes in normal responders, these potential advantages decrease with worsening ovarian response. Patients with poorer ovarian response do not benefit from the freeze-all strategy.

Live births after polar body biopsy and frozen-thawed cleavage stage embryo transfer: case report.

Pre-implantation genetic diagnosis (PGD) or screening (PGS) technology, has emerged and developed in the past few years, benefiting couples as it allows the selection and transfer of healthy embryos during IVF treatments. These techniques can be performed in oocytes (polar-body biopsy) or embryos (blastomere or trophectoderm biopsy). In this case report, we describe the first two live births to be published in Brazil after a polar-body (PB) biopsy. In case 1, a 42-year-old was submitted to PB biopsy with PGS due to advanced maternal age and poor ovarian reserve. Five MII oocytes underwent first and second polar body biopsy and four cleavage embryos were cryopreserved. The PGS analysis resulted in two euploid embryos (next generation sequence). A frozen-thawed embryo transfer (FET) was performed after endometrial priming and a healthy baby was delivered after a cesarean section (37 weeks, female, 3390g, 47.5 cm). In case 2, a 40-year old patient with balanced translocation and poor ovarian response was submitted to PB biopsy. Two MII oocytes underwent first and second polar body biopsy and two embryos were cryopreserved in cleavage stage. The analysis resulted in one euploid embryo that was transferred after endometrial priming. A preterm healthy baby (34 weeks, female, 2100g, 40 cm) was delivered via cesarean section. In conclusion, although the blastocyst biopsy is the norm when performing PGS/PGD during IVF treatments, other alternatives (as PB biopsy) should be considered in some specific situations.

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

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; I(2) = 0%) and RR = 1.38 (95% CI: 1.05-1.83; I(2) = 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.

Ratio of progesterone-to-number of follicles as a prognostic tool for in vitro fertilization cycles.

PURPOSE: To establish a ratio of the P level to the number of follicles (P/F ratio) on the day of human chorionic gonadotropin (hCG) administration and to evaluate whether this ratio is associated with in vitro fertilization (IVF) outcome. METHODS: This study was conducted between January 2012 and June 2013. A total of 337 patients with cleavage-stage day-3 fresh embryo transfer with P levels ≤1.5 ng/mL on the day of hCG administration were included in the study. The main outcome was ongoing pregnancy rate. RESULT(S): The P/F ratio was calculated according to the equation (P[ng/mL]/number of follicles) on the day of final oocyte maturation. Using ROC, we established a cut-off level of 0.075 for the P/F ratio. The area under the curve (AUC) (0.756; 95 % confidence interval [CI]: 0.704-0.807) indicated that it was a good prognostic test. In group 1 (patients under 36 years old), the ongoing pregnancy rates were 57 and 30 % for patients with P/F ratios ≤ .075 and > .075, respectively, (p = 0.003). In group 2 (patients between 36 and 39 years old), the ongoing pregnancy rates were 58 % and 17 % (p = 0.001) for patients with P/F ratios ≤ .075 and > .075, respectively. In group 3 (patients ≥ 40 years old), the ongoing pregnancy rates were 41.7 and 10.9 % (p = 0.001) for patients with P/F ratios ≤ .075 and > .075, respectively. CONCLUSIONS: The P/F ratio is a good prognostic test for predicting IVF outcome that can correlate the P level with ovarian response.

Freeze-all policy: fresh vs. frozen-thawed embryo transfer.

OBJECTIVE: To compare in vitro fertilization (IVF) outcomes between fresh embryo transfer (ET) and frozen-thawed ET (the "freeze-all" policy), with fresh ET performed only in cases without progesterone (P) elevation. DESIGN: Prospective, observational, cohort study. SETTING: Private IVF center. PATIENT(S): A total of 530 patients submitted to controlled ovarian stimulation (COS) with a gonadotropin-releasing hormone-antagonist protocol, and cleavage-stage, day-3 ET. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Ongoing pregnancy rates. RESULT(S): A total of 530 cycles were included in the analysis: 351 in the fresh ET group (when P levels were ≤1.5 ng/mL on the trigger day); and 179 cycles in the freeze-all group (ET performed after endometrial priming with estradiol valerate, at 6 mg/d, taken orally). For the fresh ET group vs. the freeze-all group, respectively, the implantation rate was 19.9% and 26.5%; clinical pregnancy rate was 35.9% and 46.4%; and ongoing pregnancy rate was 31.1% and 39.7%. CONCLUSION(S): The IVF outcomes were significantly better in the group using the freeze-all policy, compared with the group using fresh ET. These results suggest that even in a select group of patients that underwent fresh ET (P levels ≤1.5 ng/mL), endometrial receptivity may have been impaired by COS, and outcomes may be improved by using the freeze-all policy.

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.

Effects of transfer of embryos independently cultured in essential and sequential culture media on pregnancy rates in assisted reproduction cycles.

PURPOSE: Several culture media are available to be used in ART. However it is uncertain whether embryos would preferably benefit from one type of medium or the association of different media. METHODS: We performed this study to evaluate the impact of simultaneous transfer of embryos independently cultured in two distinct culture media, on pregnancy outcome. A total of 722 couples who underwent infertility treatment were sequentially allocated into three groups: those who had half of the embryos individually cultured in MEM and the other half cultured in sequential media (MEM + Seq Group) (n = 243); those who had all embryos cultured only in sequential medium (Seq Group) (n = 239); and those who had all embryos cultured only in MEM (MEM Group) (n = 240). RESULTS: The pregnancy rate was higher in the MEM + Seq group (51.8 %) than the Seq group (36.7 %) (p < 0.001). However the pregnancy rate observed in the MEM group was similar to the others (44.2 %). When a logistic regression test was applied it demonstrated that the number of transferred embryos did not interfere in the pregnancy rates. CONCLUSIONS: Our results suggests that offering different culture conditions for sibling embryos with subsequent transfer of embryos that were kept in distinct culture media, might increase pregnancy rates in assisted reproduction cycles.

Birth of normal infants after transfer of embryos that were twice vitrified/warmed at cleavage stages: report of two cases.

The role of cryopreservation in assisted reproductive technology programs has increased within the last years allowing the transfer of a limited number of embryos and the storage of the remaining for future use. The reduction in the number of transferred embryos decreases the frequency of multiple pregnancy rates and of ovarian hyperstimulation syndrome while the cumulative pregnancy rate can be maximized. Moreover, as not all embryos will survive the warming process more cleavage stage embryos are warmed to improve selection for transfer. Therefore, surplus good quality cleavage stage embryos and/or blastocysts must be re-vitrified for further transfer to achieve pregnancy. To our knowledge, there have been no reports demonstrating that human embryos can be successfully vitrified/warmed twice at the cleavage stage. Thus we report two successful pregnancies and deliveries of healthy babies after transfer of embryos that were twice vitrified/warmed at 2-4 cells stage.

Metabolismo embrionário no período pré-implantação / Preimplantation embryo metabolism

Há décadas os pesquisadores tentam elucidar as bases fisiológicas e metabólicas do desenvolvimento embrionário. No que diz respeito ao período pré-implantação, a maior parte das informações foi obtida a partir de estudos com modelos animais devido, sobretudo aos impedimentos éticos e legais envolvidos na pesquisa com embriões humanos. Frequentemente, os trabalhos sobre desenvolvimento embrionário pré-implantação envolvem temas como requerimento energético, atividade mitocondrial, controle da expressão gênica, biossíntese de macromoléculas, comunicação intra e intercelular e resposta ao estresse. Entender como se dá o desevolvimento de blastocistos de alta qualidade é de grande importância para melhorar as condições de cultivo de embriões e, conseqüentemente, aumentar o sucesso dos ciclos de reprodução assistida. Neste estudo serão descritos os principais aspectos do desenvolvimento embrionário desde a fecundação até o estágio de blastocisto. Serão enfocadas as principais necessidades metabólicas, de que maneira a cultura de embriões em ART supre estas necessidades e as conseqüências do desenvolvimento in vitro no metabolismo embrionário.