Survey on the Impact of COVID-19 on the Practice of Assisted Reproduction in Latin America.

OBJECTIVE: To follow the impact of the SARS-CoV-2 pandemic on the practice of assisted reproductive technology in centers reporting to the Latin American Registry during 2020. METHODS: An internally validated online survey designed on the Survey Monkey platform with a maximum of 20 closed questions was sent via e-mail or WhatsApp to the clinical director of each center reporting to the Latin American Registry of Assisted Reproduction between July and December 2020. RESULTS: The number of centers responding to the survey varied during the six months. The relative contribution of Brazil to all responses was 41.4% to 45%, followed by México (16.2% to 23.8%), Argentina (8.1% to 12.6%), Colombia (7.1% to 8.2%), Chile (3.6% to 6.1%) and Peru (4.0% to 4.9%). Most centers reported stopping activities before July 2020 (81%). COVID-19 related symptoms were a criterion on their own to postpone ovarian stimulation (80.1% to 87.7% of centers). Although in July only 76 of 166 centers (45.8%) performed embryo transfers, by October 104 of 109 centers (95.4%) performed them. In survey 6 (December), 78 of 79 centers (98.7%) that had initially closed had already reopened, although 62.3% (61 of 98 centers) still performed 80% or less of their usual number of ART cycles. CONCLUSIONS: Most centers modified their clinical practice and applied specific protocols to screen their staff and patients. Suspicion of COVID-19 delayed treatments. Despite a peak of the pandemic, by December most centers were performing all ART treatments, although the number of cycles remained low compared to pre-pandemic numbers.

Assisted reproductive technologies in Latin America: the Latin American Registry, 2019.

RESEARCH QUESTION: What was the utilization, effectiveness and safety of assisted reproductive technology (ART) in Latin America during 2019? DESIGN: This was a retrospective collection of multinational data on ART performed at 196 institutions from 15 countries. RESULTS: A total of 106,918 initiated cycles, 18,133 deliveries and 21,096 births were reported. ART utilization was 24-558 cycles per million inhabitants. Women aged ≥40 years represented 32.9% of fresh IVF and intracytoplasmic sperm injection (ICSI) cycles. After removing freeze-all cycles, the delivery rate per oocyte retrieval was 17.3% for ICSI and 19.5% for IVF. Overall, single-embryo transfer (SET) represented 36.2% of fresh transfers, with a 19.5% delivery rate per transfer, increasing to 30.7% for elective SET and 32.7% for blastocyst elective SET (eSET). The delivery rate for double-embryo transfers (DET) was 27.8%, increasing to 37.1% after elective DET. This 6.4% increment in deliveries between eSET and elective DET resulted in a 12-fold increase in twin births. Furthermore, overall perinatal mortality was more than two-fold higher for twin compared with singleton deliveries. The delivery rate for frozen-thawed SET reached 28.1%, most being blastocyst transfers. Of all births, 72.3% were singletons, 26.4% twins and 1.3% triplets and higher multiples. Preterm deliveries reached 14.3% for singletons and 58.1% for twins. Perinatal mortality was 7.4‰ in singletons, 17.2‰ for twins and 62.9‰ for triplets or higher. CONCLUSIONS: The number of initiated cycles has slowly increased in countries with laws or regulations facilitating access. FET cycles predominate and blastocyst SET are also increasing. The data show that, especially in young women and oocyte recipients, when there is more than one blastocyst for transfer, eSET should be the rule.

Celebrating 30 years of ART in Latin America; and the 2018 report.

OBJECTIVE: What are the trends in patient characteristics, effectiveness and safety of assisted reproductive technology (ART) performed in Latin America over the past three decades, as well as the detailed outcomes of procedures initiated in 2018?. DESIGN: Retrospective collection of multinational data including epidemiology and outcomes of ART performed between 1990 and 2018. RESULTS: Over these 30 years we report 955,117 initiated cycles, 191,191 deliveries and 238,045 live births. In 1990, 66.5% of women were ≤34 years and 8.7% ≥40 years; in 2018, 26.4% of women were ≤34 years and 32.0% were ≥40 years. In 1990, 60.4% of transfers included ≥3 embryos, falling to 13.5% in 2018, and single embryo transfer (SET) increased from 13.8% to 30.4% between 1990 and 2018. Delivery rate per fresh transfer increased from approximately 17% in the 1990s to 25% in 2018, with a meaningful drop in high-order multiples, from 5-9% in the 1990s to 0.4% in 2018. This drop is associated with increasing use of frozen embryo transfer (FET) (57% in 2018) compared with 10% in 2000. In 2018, delivery rate in FET was 28.3%, reaching 31.2% in freeze-all cycles; and the cumulative live birth rate (fresh + FET) was 41.9%. Elective SET also increased, from 0.9% in 2010 to 10% in 2018. The delivery rate in elective SET (31.7%) was only 5.4% lower than elective double embryo transfer (DET) (37.1%); however, multiple births increased from 2.1% to 25.5% twins and 0.4% triplets in elective DET. CONCLUSIONS: The Latin American Registry of Assisted Reproduction (RLA) celebrates 30 years of voluntary reporting from a total of nearly 200 centres in 15 countries. This South-South Cooperation network has proven to be an efficient and safe system for technological transfer and regional growth.

Successful pregnancy after ovulation induction with human chorionic gonadotropin in a woman with selective luteinising hormone deficiency.

Selective LH deficiency has been described in several men, but only in two women who presented normal pubertal development but secondary amenorrhoea due to anovulation. Despite its rarity, this condition represents a valuable model for studying the processes regulated by FSH or LH during late folliculogenesis and ovulation in humans. A woman previously diagnosed with selective LH deficiency due to a homozygous germline splice site mutation in LHB (IVS2 + 1G→C mutation) was submitted to an individualised ovarian induction protocol, first with recombinant LH and then with highly purified urinary hCG. Ovarian follicle growth and ovulation were achieved, and a healthy baby was born after an uneventful term pregnancy. The treatment described herein demonstrates that the clinical actions of exogenous LH or hCG in inducing late-stage follicular development in women with deficient LH production or performance might be interchangeable or inevitable, once FSH-dependent early follicular growth is assured.

Assisted reproductive technology in Latin America: the Latin American Registry, 2017.

RESEARCH QUESTION: What was the utilization, effectiveness and safety of assisted reproductive technologies (ART) carried out in Latin America during 2017. DESIGN: Retrospective collection of multinational data on ART carried out in 188 institutions from 15 Latin American countries. RESULTS: In this study, 93,600 initiated cycles, 16,976 deliveries and 20,404 births reported. Utilization of ART was 221 cycles per million inhabitants (15 to 535). Women aged 40 years and above represented 30.5% of fresh IVF and intracytoplasmic sperm injection (ICSI); however, 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 elective DET over elective SET resulted in a tenfold increase in twin births, gestational periods almost 3 weeks' shorter and a threefold increase in perinatal mortality. Delivery rate in frozen-thawed SET reached 25.5% increasing to 30.8% with DET, most being blastocyst transfers. Of all births, 66.9% 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; perinatal mortality was 9.4‰ in singletons, 25.3‰ in twins and 63.3‰ in high-order multiples. CONCLUSIONS: The number of initiated cycles has slowly increased. Frozen embryo transfers, blastocyst transfers and SET are also increasing. Our data show that, especially in young women and oocyte recipients, when there is more than one blastocyst for transfer, elective SET should be the rule.

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.

Survey of Third-Party Parenting Options Associated With Fertility Preservation Available to Patients With Cancer Around the Globe.

Purpose: In the accompanying article, "Survey of Fertility Preservation Options Available to Patients With Cancer Around the Globe," we showed that specific fertility preservation services may not be offered at various sites around the world because of cultural and legal barriers. We assessed global and regional experiences as well as the legal status of third-party reproduction and adoption to serve as a comprehensive international data set and resource for groups that wish to begin oncofertility interventions. Methods: We provide data on the legalities of third-party assisted reproductive technologies and other family-building options in the 28 oncofertility-practicing countries surveyed. Results: We found regional and country differences that will be important in the development of tailored resources for physicians and for patient brochures that are sensitive to these local restrictions and cultural norms. Conclusion: Because many patients first consult Web-based materials, the formal assessment of the availability of these options provides members of the global oncofertility community with data to which they might otherwise not have ready access to better serve their patients.

Survey of Fertility Preservation Options Available to Patients With Cancer Around the Globe.

Purpose: Oncofertility focuses on providing fertility and endocrine-sparing options to patients who undergo life-preserving but gonadotoxic cancer treatment. The resources needed to meet patient demand often are fragmented along disciplinary lines. We quantify assets and gaps in oncofertility care on a global scale. Methods: Survey-based questionnaires were provided to 191 members of the Oncofertility Consortium Global Partners Network, a National Institutes of Health-funded organization. Responses were analyzed to measure trends and regional subtleties about patient oncofertility experiences and to analyze barriers to care at sites that provide oncofertility services. Results: Sixty-three responses were received (response rate, 25%), and 40 were analyzed from oncofertility centers in 28 countries. Thirty of 40 survey results (75%) showed that formal referral processes and psychological care are provided to patients at the majority of sites. Fourteen of 23 respondents (61%) stated that some fertility preservation services are not offered because of cultural and legal barriers. The growth of oncofertility and its capacity to improve the lives of cancer survivors around the globe relies on concentrated efforts to increase awareness, promote collaboration, share best practices, and advocate for research funding. Conclusion: This survey reveals global and regional successes and challenges and provides insight into what is needed to advance the field and make the discussion of fertility preservation and endocrine health a standard component of the cancer treatment plan. As the field of oncofertility continues to develop around the globe, regular assessment of both international and regional barriers to quality care must continue to guide process improvements.

Embryo placement in IVF and reproductive outcomes: a cohort analysis and review.

OBJECTIVE: The objective of the present study was to determine the influence of the embryo placement depth on the endometrial cavity in relation to the reproductive outcomes, after frozen-thawed embryo transfer performed under transabdominal ultrasound guidance. METHODS: Retrospective cohort study that evaluated the influence of the embryo placement depth in the endometrial cavity in relation to the reproductive outcomes of patients submitted to cryotransfer cycles at a private assisted reproduction clinic, from 2012 to 2017. The patients were classified according to three variables: <10mm, 10 to 15mm and >15mm. The primary outcome was clinical pregnancy, and the secondary outcomes were miscarriage, ongoing pregnancy and live birth. The data was summarized as relative risk, with a 95%CI. RESULTS: Clinical and ongoing pregnancy rates were higher in the 10-15mm and >15mm Groups, when compared to the <10mm Group; there was no statistical difference between the groups in terms of miscarriage and live birth rates. We performed a subsequent analysis, using the same sample of patients, comparing only the <10mm and ≥10mm variables. The ≥10mm Group had better reproductive outcomes, with higher clinical and ongoing pregnancy rates. CONCLUSION: Pregnancy rates are influenced by embryo transfer site, and better results can be achieved when the tip of the catheter is placed in the central area of the endometrial cavity, especially when the distance from the endometrial fundus is >10mm.

Corifollitropin alfa compared to daily rFSH or HP-HMG in GnRH antagonist controlled ovarian stimulation protocol for patients undergoing assisted reproduction.

OBJECTIVE: This study aimed to compare the outcomes of controlled ovarian stimulation (COS) with corifollitropin alfa versus daily recombinant follicle-stimulating hormone (rRFSH) or highly purified human menopausal gonadotropin (HP-HMG) in patients undergoing in vitro fertilization (IVF) cycles based on gonadotropin-releasing hormone (GnRH) antagonist protocols. The primary endpoints were total number of oocytes and mature oocytes. METHODS: This retrospective study looked into 132 controlled ovarian stimulation cycles from IVF or oocyte cryopreservation performed in a private human reproduction center between January 1 and December 31, 2014. Enrollment criteria: women aged < 40 years submitted to COS with corifollitropin alfa 100µg or 150µg (n = 26) and rFSH or HP-HMG in the first seven days of treatment with daily doses of 150-225 IU (n = 106); all subjects were on GnRH antagonist protocols. RESULTS: The groups had similar mean ages and duration of stimulation. The mean number ± standard deviation of total aspirated oocytes and MII oocytes was 11.9±10 and 10.3±7.9 in the corifollitropin alfa group, and 10.9±7.2 and 8.6±5.7 in the group on rFSH or HMG (p>0.05). There were no significant differences in fertilization (76.9% vs. 76.8%, p=1.0), biochemical pregnancy (66.7% vs. 47.2%, p=0.1561) or embryo implantation rates (68.7% vs. 50%, p=0.2588) between the groups using corifollitropin alfa and rFSH or HMG, respectively. CONCLUSIONS: Corifollitropin alfa seems to be as effective as rFSH or HP-HMG when used in the first seven days of ovulation induction for patients undergoing assisted reproduction in GnRH antagonist protocols.

Indução de ovulação em pacientes com tumor estrogênio­dependente: diretrizes clínicas da Sociedade Brasileira de Reprodução Humana / Ovulation induction in patients with estrogen­dependent tumors: a Brazilian Society of Human Reproduction clinical practice guideline

A oncofertilidade é um campo de interesse interdisciplinar de desenvolvimento recente que busca mesclar os conhecimentos em oncologia e medicina reprodutiva, com a contribuição das técnicas de reprodução assistida, para o desenvolvimento de estratégias de preservação da função gonadal e oferecer a possibilidade da procriação biológica aos sobreviventes de câncer. As estratégias de preservação da fertilidade feminina em pacientes oncológicas atualmente aceitas para a prática rotineira são a criopreservação de embriões e a criopreservação de oócitos maduros. Ocorre que, para execução de ambos, a indução de ovulação é obrigatória e, com ela, vêm os riscos teóricos de estimulação do crescimento de tumores estrogênio­dependentes e a postergação do início do tratamento antineoplásico. Os protocolos de estimulação ovariana de início aleatório contemplam a intenção de se minimizar o atraso no início da quimioterapia ou radioterapia e o bloqueio ao crescimento tumoral e oferecem resultados satisfatórios, semelhantes aos obtidos em protocolos de início habitual. Apresentamos neste artigo as diretrizes clínicas da Sociedade Brasileira de Reprodução Humana para indução de ovulação em pacientes com tumor estrogênio­dependente.(AU)

Oncofertility is an interdisciplinary interest field of recent development, which aims to merge the knowledge in oncology and reproductive medicine, with the help of assisted reproductive technologies, to develop strategies for gonadal function preservation and to offer the possibility of biological procreation to cancer survivors. Preservation strategies of female fertility in oncological patients currently accepted for routine practice are the cryopreservation of embryos and cryopreservation of mature oocytes. It happens that ovulation induction is mandatory for executing both strategies, and with it the theoretical risk of stimulation of estrogen­dependent tumors growth and the postponement of anti­neoplastic treatment. Random­start ovarian stimulation protocols include the intention of minimizing the delay in onset of chemo­radiotherapy and to block tumor growth, providing satisfactory results, similar to those obtained in the usual beginning protocols. This article presents the clinical guidelines of the Brazilian Society of Human Reproduction for ovulation induction in patients with estrogen­dependent tumors.(AU)

The association between follicular size at the time of spontaneous rupture and pregnancy rates in clomiphene citrate treated PCOS patients in coit cycles.

OBJECTIVE: To investigate the follicular size at spontaneous rupture on pregnancy rate in patients with polycystic ovary syndrome (PCOS) undergoing clomiphene citrate (CC) ovulation. DESIGN: Cross-sectional study. PATIENTS AND METHODS: One hundred and four women with ovulatory cycles after use of CC followed by ultrasound to determine the follicle size at the time of rupture, which was subsequently correlated with the occurrence of pregnancy or not in coit cycles. RESULTS: In the group of follicular rupture at a mean diameter ≤25 mm (n = 54), pregnancy rate was 35.1% and when follicular rupture occurred at a mean diameter >25 mm (n = 50), it was 34% (p > 0.05). When different diameters at follicular rupture were randomly correlated with the pregnancy rate, there was no significant difference. CONCLUSION: Our data suggest that the occurrence of pregnancy after ovulation induction with CC in women with PCOS is not associated with follicle size at the time of rupture.

Ovarian reserve assessment for infertility investigation.

The current trends to postpone motherhood and the increase in demand for assistance in reproductive medicine highlight the need for seeking guidelines for the establishment of individualized treatment protocols. Currently available ovarian reserve tests do not provide sufficient evidence to be solely considered ideal, but they may occupy important place in initial counseling, predicting unsatisfactory results that could be improved by individualized induction schemes and reducing excessive psychological and financial burdens, and adverse effects. In this paper, we revise the role of hormonal basal and dynamic tests, as well as ultrasonographic markers, as ovarian reserve markers, in order to provide embasement for propaedeutic strategies and their interpretation in order to have reproductive success.

Avaliação genética pré-implantacional: visão geral / Preimplantation genetic testing: an overview

Identificar um embrião com alto potencial de implantação é um dos maiores desafios da medicina reprodutiva e um passo fundamental em direção à transferência de um único embrião. O diagnóstico genético pré-implantacional permite identificar alterações genéticas ou cromossômicas nos embriões em divisão antes de serem transferidos, enquanto o rastreamento genético pré-implantacional realiza a triagem em embriões quanto às anomalias cromossômicas frequentes. Dentre as limitações encontradas, o mosaicismo é responsável por grande parcela de erros de diagnóstico, e os altos custos das técnicas de hibridização in situ por fluorescência e reação em cadeia da polimerase ainda dificultam a implantação do diagnóstico genético pré-implantacional e do rastreamento genético pré-implantacional de forma rotineira. Este artigo pretende apresentar uma visão geral acerca das modalidades de avaliação genética préimplantacional disponíveis e seus resultados e avaliar criticamente a inserção dessas tecnologias entre os recursospropedêuticos para assistência reprodutiva.

The identification of an embryo with high implantation potential is one of the greatest challenges in reproductive medicine and a vital step towards transferring a single pre-embryo. Preimplantation genetic diagnosis allows the identification of genetic or chromosomal alterations in pre-embryos before they are transferred to the uterus, while preimplantation geneticscreening determines alleatory frequent chromosomal abnormalities. Among limitations, mosaicism is responsible for a large proportion of misdiagnosis, and the high costs of fluorescent in situ hybridization and polymerase chain reaction still hinder the implementation of preimplantation genetic diagnosis and preimplantation genetic screening as a routine. Thisarticle aims to present an overview of possible modalities of preimplantation genetic evaluation and their results and to criticallyevaluate the insertion of those technologies in the propaedeutical tools in reproductive assistance.

Estudo multicentro da eficácia e segurança da lomefloxacina versus sulfametoxazol/trimetoprim no tratamento de cistite em mulheres / Multicenter study on the efficacy and safety of lomefloxacin versus trimethoprim and sulfamethoxazole in the treatment of lower urinary tract infection in women

A lomeflomexacina (maxaquim), uma nova quinolona difluorada, e o trimetoprim/sulfametoxazol (bactrim) foram comparados no tratamento de mulheres adultas com infecçöes urinárias simples. O estudo foi randomizado, prospectivo, controlado e realizado em seis centros. Um total de 57 pacientes foram estudados: 30 em tratamento com Bactrim e 27 em tratamento com Maxaquim. As pacientes receberam 400mg de lomefloxacina via oral, de 12/12 horas, por três dias ou 160mg/800mg trimetoprim/sulfametoxazol via oral, de 12/12 horas por sete dias. Eschericia coli, Klebsiella e Proteus mirabilis foram os patogenos mais frequentemente isolados. Cinco a nove dias pós-terapia, cura bacteriológica foi verificada em 92,6 por cento das pacientes tratadas com lomefloxacina e em 90 por cento das pacientes do grupo do trimetoprim/sulfametoxazol. Sucesso clínico foi constatado em 96,3 por cento das pacientes no grupo da lomefloxacina e em 96,7 por cento das pacientes trimetoprim/sulfametaxol. Efeitos adversos, provavelmente relacionados com o tratamento, foram nauseas, desconforto gástrico de moderada intensidade e mal estar com nauseas de forte intensidade para o grupo trimetoprim/sulfametoxazol e epigastralgia de fraca intensidade para o grupo lomefloxacina. O tratamento único com lomefloxacina foi eficaz e bem tolerado no tratamento das infeçöes do trato urinário causadas por patogenos sensíveis a esta droga

O papel da curva de temperatura basal no diagnóstico de endometriose / The basal body temperature curve in diagnostic of endometriosis

Este estudo analisa a ocorrência de declínio tardio da curva de temperatura corpórea basal (CTBsal) no período menstrual de 12 pacientes inférteis com diagnóstico laparoscópico de endometriose. O grupo-contrôle sem endometriose, pela avaliaçäo laparoscópica, constituiu-se de 13 mulheres inférteis. Concluímos que existe uma maior incidência estatisticamente significativa de declínio tardio de CTBasal em pacientes inférteis com endometriose em relaçäo à pacientes sem endometriose