Vitamin D and follicular recruitment in the in vitro fertilization cycle.

OBJECTIVE: Vitamin D (VD) is a fat-soluble steroid hormone, synthesized by the skin, most known for its role in bone mineral balance. Vitamin D receptors (VDR) are also found in the female reproductive system, but their role remains unclear. The objective of this study was to analyze the relationship between serum vitamin D levels and the number of oocytes retrieved after ovarian stimulation. METHODS: This is a retrospective study involving 267 patients undergoing in vitro fertilization (IVF) carried out in the Fertipraxis clinic, a private practice facility. The patients were initially divided into two groups according to their VD levels. Group 1 included 152 patients with VD levels < 30 ng/mL and group 2 had 115 patients with VD levels > 30 ng/mL. They were further analyzed and separated considering their age, anthropometric data, ovarian reserve, amount of gonadotropin used, and follicles obtained until trigger day. RESULTS: In our analysis, there were no difference in the number of follicles and oocytes retrieved, nor in the number of mature oocytes obtained from patients with both vitamin D deficiency and sufficiency. CONCLUSIONS: The results of our study show no difference among number of follicles, oocytes retrieved and mature oocytes obtained after ovarian stimulation according to their vitamin D serum levels. Further higher-quality studies are needed to evaluate the possible roles of serum vitamin D levels in other stages of human fertilization process.

Assisted reproductive techniques in Latin America: The Latin American Registry, 2017.

RESEARCH QUESTION: What was the utilization, effectiveness and safety of assisted reproductive techniques performed in Latin America during 2017. DESIGN: Retrospective collection of multinational data on ART performed in 188 institutions from 15 Latin American countries. RESULTS: We are reporting 93,600 initiated cycles, 16,976 deliveries and the birth of 20,404 babies. ART utilization was 221 cycles/million inhabitants (15 to 535). Despite women aged ≥40 represented 30.5% of fresh IVF/ICSI, after removing freeze-all cycles, delivery rate per oocyte retrieval was 19.9% for ICSI and 20.2% for IVF. Overall, single embryo transfer (SET) represented 26.9% of fresh transfers, with 18.2% delivery rate per transfer; increasing to 32.3% in elective SET. Delivery rate in double embryo transfers (DET) was 28.3% increasing to 37.3% with elective DET. This 5% increment in births in eDET over eSET resulted in10-fold increase in twin births, almost 3 weeks' shorter gestations and 3-fold increase in perinatal mortality. Delivery rate in frozen/thawed SET, reached 25.5% increasing to 30.8% with DET; the majority being blastocysts transfers. Of all births, 67% were singletons, 31.4% twins, and 1.6% triplets and higher. Overall, preterm deliveries reached 9.5% in singletons, 64.3% in twins and 97.9% in triplets; and perinatal mortality was 9.4‰ in singletons, 25.3‰ in twins, and 63.3‰ in high-order multiples. CONCLUSIONS: The number of initiated cycles slowly increases. Frozen embryo transfers, blastocyst transfers and SET are also increasing. Our data shows that especially in young women and oocyte recipients, when there is more than one blastocyst for transfer, elective SET should be the rule.

Vaginismus in Assisted Reproductive Technology Centers: an invisible population in need of care.

OBJECTIVE: Genital and sexual pain is still neglected. Consequences may be dramatic, since infertility and sexual dysfunction may be reciprocally linked. This is the first study to focus on the identification of cases of vaginismus in the ART scenario and on the introduction of intra-cycle interventions as part of a comprehensive, integrated and patient-centered perspective. METHODS: This observational prospective study looked into 425 IVF/ICSI cycles and 226 frozen embryo transfers carried out from January 1, 2015 to December 31, 2016, and found seven cases of vaginismus. Within a six-month period, a questionnaire placed on SurveyMonkey was sent twice to 228 ART centers in Latin America. The purpose was to learn how often cases of vaginismus were found in ART centers and the perceptions around the presence of this condition. RESULTS: The few centers that took the time to answer the questionnaire (24/10.5%) stated that the number of cases in which they had trouble performing control ultrasound examination or needed to perform transfers with patients under sedation was not significant. Although 81% agreed that the incidence of these conditions is low, no references were made to cases of vaginismus, dyspareunia or sexual dysfunction. Our multidisciplinary team found seven cases of vaginismus, involving women with higher education degrees with a mean age of 37.8 years and married for a mean of four years. Although two reported they were able to tolerate intercourse, all reported undergoing treatments such as using vaginal dilators (3), psychotherapy (4) and psychiatric care (1). The care provided by the staff was designed to mitigate patient suffering. CONCLUSION: Gentle care and sensitive listening should be integral components in the work of multidisciplinary teams to identify women with vaginismus and offer couples better quality treatment.

High Progesterone levels in the beginning of ICSI antagonist cycles and clinical pregnancy: still a concern?

OBJECTIVE: In controlled ovarian hyperstimulation (COH) using antagonist cycles, an incomplete luteolysis could happen after an inefficient previous luteolysis. Since antagonist cycles are frequent today, this study aims to access the impact of serum progesterone in the beginning and at the end of stimulation, and pregnancy outcomes. METHODS: single-center cohort study, 461 fresh embryo transfers in ICSI antagonist cycles. Serum progesterone levels was measured in the beginning of COH (P4i) and on hCG day (P4f) using threshold values of 1.5ng/mL. Four groups were created: Group 1, P4i and P4f ≤ 1.5; Group 2, P4i ≤ 1.5 and P4f > 1.5; Group 3, P4i > 1.5 and P4f ≤ 1.5 and Group 4, P4i and P4f > 1.5. The clinical pregnancy rate (CPR) and live birth rates (LBR) were the primary outcomes. RESULTS: The number of cycles per group was: 393, 51, 6 and 11, respectively. Group 1 was considered the expected normal, while group 4 represented the persistence of higher levels. There was no difference in age, basal FSH and Estradiol, days of stimulation endometrium thickness and total amount of gonadotropins between group 1 versus group 4. However, significant differences occurred in embryological and clinical outcomes between these 2 groups. CONCLUSION: The impact of serum progesterone in the beginning of stimulation and pregnancy outcomes is a matter of concern. Basal elevated levels could help identify patients that will repeat it on hCG day, being probably a marker to define a freeze-all strategy to these cycles.

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.

Body weight and 25-hidroxyvitamin D follicular levels: a prospective study of women submitted to in vitro fertilization.

OBJECTIVE: Vitamin D deficiency has been largely related to infertility in animals. However, data demonstrating a direct association between hypovitaminosis D and infertility in humans are still conflicting. Increased body weight and an elevated body mass index (BMI) are known for their association with infertility. Therefore, this study attempted to verify whether increases in body weight and the BMI were associated with lower 25-hidroxyvitamin D [25(OH)D3] levels in the follicular fluid (FF) of patients treated for infertility with intracytoplasmic sperm injections (ICSI). This study aimed to assess the FF levels of 25(OH)D3 in women submitted to ICSI and correlate these levels with the different body weight and BMI values observed in the enrolled cohort. METHODS: The FF aspirates of 199 patients submitted to ICSI were collected after oocyte aspiration to check whether FF 25(OH)D3 levels were associated with weight regardless of the etiology of infertility. Chemiluminescent assays were used to assess FF 25(OH)D3 levels. The etiology of infertility was defined based on patient clinical history and follow-up. RESULTS: The patients enrolled in the study were divided into three groups according to their FF 25(OH)D3 levels, as follows: a) deficient (n=71; <20 ng/ml); b) insufficient (n=64; 21< 25(OH) D3>29 ng/ml); and c) sufficient (n=56 >30ng/ml) levels. Patients with lower FF 25(OH)D3 levels had a greater mean weight (64.1kg) when compared to patients with higher 25(OH)D3 levels (60.7kg), p<0.01. No differences were observed in terms of age or etiology of infertility. CONCLUSION: The body weight of the individuals with FF 25(OH)D3 deficiency measured in single follicles was significantly higher regardless of the etiology of infertility. Further epidemiologic and molecular studies are required to verify whether the amount of follicular 25(OH)D3 affects the outcome of IVF procedures.

Zika virus and Assisted Reproductive Technology: to test or not to test, that is the question. Is it an unnecessary cost? The first two months of mandatory testing in an outbreak area in Rio de Janeiro, Brazil.

OBJECTIVE: Infection by the Zika virus is a Public Health Emergency of International Concern as defined by the World Health Organization. Resolution no. 72, issued by the Collegiate Board of the Brazilian Health Surveillance Agency (ANVISA) on March 30, 2016, made ZKV testing mandatory prior to procedures involving germ cells and tissues. This paper aims to discuss the aforementioned Resolution from the standpoint of evidence and cost-effectiveness of the measures taken within the first two months of mandatory testing. METHODS: The medical staff at the clinic looked into the steps needed to comply with the new rules and checked laboratories in the city to perform the tests with their lead times and costs, health insurance refunds, data maintenance capabilities, how to contact patients, decision-making processes in ongoing cases, deadlines for implementation, in addition to exchanging ideas with other clinics and gathering information from the guidelines being produced. A SWOT analysis was performed. RESULTS: A total of 152 tests were performed within the first two months of mandatory testing, in five different clinical situations: one previously symptomatic woman with a negative PCR test before starting the cycle; two asymptomatic women had positive IgM (1.3%) and negative PCR tests on days 25 and 60; one husband enrolled as a suspect with a negative RT-PCR on day 13 and another untested suspected case; a couple decided to have their oocytes cryopreserved because the husband's test result was not available on pickup day. The mean cost of USD 200 per couple is equivalent to 1.2 day of the stimulation protocol. The staff worked more efficiently and was able to respond promptly to the increased demand for ZKV testing; however, the tests failed to reassure patients of the safety of the procedure and increased costs. CONCLUSION: The testing requirement for asymptomatic patients prior to ART should be reviewed.

Prediction of metaphase II oocytes according to different serum Anti-Müllerian hormone (AMH) levels in antagonist ICSI cycles.

OBJECTIVE: This paper aims to assess a qualitative aspect of ovarian response in terms of metaphase II oocytes according to different serum Anti-Müllerian hormone levels in antagonist ICSI cycles. A prediction index might contribute to the individualization of care. METHODS: This observational study looked into 287 antagonist ICSI cycles carried out with patients treated in a single center between January of 2012 and January of 2016. Serum AMH and subgroup analyses were performed based on five AMH ranges (≤ 0.3 ng/mL;> 0.3 and ≤ 0.7 ng/mL; > 0.7 and ≤ 1.0 ng/mL; > 1.0 and < 3.0 ng/mL; ≥ 3.0 ng/mL). The variables analyzed included patient age; serum FSH and antral follicle count at the start of the cycle; number of stimulation days and number follicles ≥ 15 mm on hCG day; number of oocytes retrieved and number of metaphase II oocytes. RESULTS: AMH is a better predictor of ovarian response to controlled ovarian stimulation than AFC or serum FSH, while age is an independent marker. AMH levels ≤0.70 (patients with poor prognosis) were observed in 140 patients (48.7%). Patients within this AMH level range accounted for 92% of the 24 failed cycles (cancelled cycles, no oocytes or immature oocytes retrieved). CONCLUSION: AMH predicts the quality of ovarian response to stimulation, regardless of patient age. Women with AMH levels ≥1.0 and ≤3.0 ng/mL are probably normal responders with good prognosis. Clinical application relies on the examination of the data from each individual center and on the establishment of correlations between AMH levels and ovarian response in the form of metaphase II oocytes.

Latin America and access to Assisted Reproductive Techniques: A Brazilian perspective.

INTRODUCTION: In Brazil, as in all Latin America, access to infertility care, including assisted reproductive technology (ART) is on debate. This paper evaluates the availability and access of Brazilian couples to ART services. METHODS: It is a qualitative study conducted about the Brazilian possibilities of ART in the public sector. A questionnaire was sent by e-mail to 14 public centers identified as providing ART (IVF/ICSI and/or IUI), with questions about their performance on 2013. The questionnaire was objective with seven questions. It was asked the number of patients seen for 1st time in 2013, and number IVF procedures and/or IUI in this interval, the source of funds to support the center, the input source of the patients, who pays for medications and how much (%), number of cycles or age limitations, whether or not oocyte donation is held. RESULTS: There were 11 answers out of 14 and during 2013 in public centers were performed 1088 IUI cycles plus 4044 IVF/ICSI cycles. The waiting lists of patients can vary from 300 to 1500 and wait from 6 months to 4 years. CONCLUSIONS: As infertility goes, charges remain incompatible with the financial possibilities of the majority of Brazilian population. The Brazilian government should consider buying cycles in private accredited centers to offer ART procedures at no cost to low-income populations. Other possibility is to state as mandatory that Health Insurance Assistance Companies cover ART treatments, making it accessible for a large part of the population.

Assisted Reproductive Technologies (ART) in Latin America: The Latin American Registry, 2012.

OBJECTIVE: This report examines information on Assisted Reproduction Technologies performed in Latin America (LA) during 2012. METHODS: Multinational data were collected directly from 155 institutions in 14 countries. Individualized, case-bycase data include 47,326 ART cycles covering more than 80% of cycles performed in LA. Treatments included in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), frozen embryo transfers (FET), oocyte donations (OD) and fertility preservation. RESULTS: In 39% of ET IVF/ICSI was performed in women age 35-39 and 31% in women ≥40 years. Delivery rate (DR) per pick-up (OPU) in ICSI and IVF cycles, were 20.9% and 26.5%, respectively. Overall multiple births comprised 20.6% twins and 1.2% triplets. Furthermore, in OD, twins and triplets reached 27.8% and 2.4%, respectively. Pre term births in singletons were 14%. The relative risk of prematurity increased by 4.30 (95% CI 4.1-4.6) in twins, and 43.8 (95% CI 28.5-67.4) in ≥ triplets. Perinatal mortality increased from 25.2‰ in singletons, to 44.0‰ in twins and 80‰ in ≥ triplets. Elective single embryo transfer (eSET) was performed in only 1.4% of cycles with DR of 30% in women ≤34 years. CONCLUSION: Trends over the last 20 years show that eSET should be the way to go provided access is facilitated with public funding.

Evaluation of two incubation environments--ISO class 8 versus ISO class 5--on intracytoplasmic sperm injection cycle outcome.

OBJECTIVE: To evaluate the impact of two different incubation environments-class 8 versus class 5-on embryo quality and pregnancy rate. DESIGN: Retrospective comparative study. SETTING: Private fertility and gynecology clinic. PATIENT(S): 123 consecutive intracytoplasmic sperm injection (ICSI) cycles were analyzed from January 2002 to February 2005. Cycles were divided into two groups: in group I (n = 60), the embryo culture was performed in class 8 air quality; in group II (n = 63), the embryo culture was performed in class 5 air quality. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Number of embryos available for transfer, number of good quality embryos transferred, implantation rate, and clinical pregnancy. RESULT(S): Age of women, duration of stimulation, total doses of gonadotropins, endometrial thickness on the day of human chorionic gonadotropin (hCG) administration, number of oocytes metaphase II retrieved, number of embryos available, number of good quality embryos transferred, fertilization and cleavage rates, implantation rate, and clinical pregnancy were not statistically different between the groups. CONCLUSION(S): Our study demonstrated that incubation environment class 8 is as good as incubation environment class 5 when compared in relation to the parameters analyzed. We believe that there is still room for improvement in the overall outcome of ICSI embryos.

Laparoscopia prévia à salpingostomia: validade no planejamento pré-operatório / Laparoscopy previous to salpingostomy: validity in preoperative planning

Analisamos 53 casos de clientes matriculados no Setor de Esterilidade do Instituto de Ginecologia da Universidade Federal do Rio de Janeiro submetidas a salpingostomia, sob técnica microcirúrgica, no período de maio de 1981 a maio de 1990. Os dados relativos aos laudos laparoscópicos foram comparados aos achados no inventário pélvico durante o ato laparotômico, tomados como padrao. A laparoscopia, como simples método de observaçao, mostrou-se concordante em 52 por cento e discordante em 48 por cento. As discordâncias foram devido a erro de interpretaçao (40 por cento), limitaçao instrumental do método (44 por cento), manipulaçao das tubas na laparotomia, com lise de aderências previamente à salpingostomia, alterando os achados do nível das obstruçoes (l6 por cento). Os procedimentos endoscópicos pré-operatórios possibilitarao selecionar melhor os casos cirúrgicos, contra-indicando operaçoes quando a fertilizaçao assistida oferecer maior oportunidade de gravidez. No momento, como método de observaçao, é insubstituível na propedêutica das obstruçoes tubárias distais.

Distúrbios da fase pós-ovulatória e funçäo endometrial: um estudo clínico em esterilidade / Postovulatory phase disturbances and endometrial function: a clinical study in sterility

Estabelecemos protocolo que permitiu avaliar a eficácia do intervalo menstrual e de duas dosagens seriadas de progesterona (P) e prolactina (PRL) no diagnóstico dos distúrbios da fase lútea. Estudamos 52 clientes com fertilidade prévia comprovada e outras 79 inférteis. Todas foram submetidas à biópsia endometrial, que foi usada como padräo-ouro na avaliaçäo dos testes estatísticos realizados. O datamento endometrial mostrou 55,8 por cento do endométrio secretor normal na populaçäo fértil, contra 27,8 por cento na populaçäo infertil. Houve 45,6 por cento de endométrio secretor deficiente do tipo dissociado entre as inférteis, de acordo com a classificaçäo de Dallenbach-Hellweg. Das 79 clientes inférteis, 42 foram submetidas à colheita de duas amostras para dosagens de P e PRL no meio da fase lútea e três dias após. O intervalo menstrual mostrou-se altamente específico, ou seja, quando de 28-30 dias raramente está associado à fase lútea deficiente. O valor preditivo positivo dos valores de P foi de 82 por cento, näo havendo diferença significativa entre os dias de colheita ou diferentes níveis de corte avaliados (< 2,3 ou ó 5ng/ml). A somatória das dosagens seriadas näo trouxe qualquer vantagem em relaçäo à dosagem única. O valor preditivo positivo da dosagem de PRL foi de 77 por cento, näo havendo diferenças significativas também entre os dias de colheita, pontos de corte ( < 2,6 ou ò 25ng/ml < 2,6 ou ò 15ng/ml ) ou avaliaçäo de quaisquer níveis alterados. Entretanto, a sensibilidade na avaliaçäo individual das colheitas favoreceu o ponto de corte que inclui valores alterados < 2,6 e ò 15 ng/ml. As dosagens hormonais mostram-se eficazes na avaliaçäo do funcionamento do corpo lúteo e podem substituir a biópsia de endométrio quando ela näo é possível de ser realizada