Switching from cetrorelix to dydrogesterone in an IVF cycle - a new strategy for unexpected freeze-all cycles.

Preventing a luteinizing hormone (LH) surge is a major concern in controlled ovarian stimulation (COS). Several strategies have been developed over the years, including protocols with Gonadotrophin Releasing Hormone agonists and antagonists. More recently Progestin Primmed Ovarian Stimulation (PPOS) has shown to be equally effective in pituitary suppression, with comparable clinical and laboratorial outcomes. This is the case of a 34 year old female, with a previous diagnosis of primary infertility due to tubal factor and high ovarian reserve markers. The initial plan was to perform IVF/ICSI. followed by fresh blastocyst transfer. The chosen COS strategy was to use Alfacorifolitropin 150mg (Elonva®) and Cetrorelix acetate 0,25mg (Cetrotide®) in a flexible pituitary suppression protocol. However, because of elevated risk for Ovarian Hyper-stimulation Syndrome (OHSS) detected during ultrasound and hormonal monitoring, in order to diminish financial burden and to have a more patient friendly protocol, we switched cetrorelix acetate to oral dydrogesterone. COS was successful and resulted in 24 retrieved oocytes (16 metaphase 2 oocytes) without any premature LH peak. No OHSS symptoms occurred. Our main goal with this case report is to reinforce the feasibility and efficacy of this innovative approach, especially in patients aiming for a fresh embryo transfer, who present alert sings of OHSS during the stimulation. Developing friendlier and cheaper protocols in assisted reproduction makes the treatment more accessible and affordable.

Delphi consensus on add-ons and social midia in Assisted Reproductive Technology.

This article reports the annals of a national consensus meeting on add-ons and social networks in Assisted Reproduction Techniques (ART). The panel of experts has developed a set of consensus points and this document is intended to be referenced as a national consensus to allow social networks and add-ons to be used in ART, following the standards of the Code of Medical Ethics and the Federal Council of Medicine, in a safe ethical and responsible way.

Metabolomic analysis of follicular fluid from women with Hashimoto thyroiditis.

Hashimoto thyroiditis is an autoimmune disease characterized by hypothyroidism and a high level of anti-thyroid autoantibodies. It has shown to negatively impact female fertility; however, the mechanisms are unclear. Ovarian follicular fluid appears to be the key to understanding how Hashimoto thyroiditis affecst fertility. Thus, we aimed to evaluated the metabolic profile of follicular fluid and antithyroid autoantibody levels in the context of Hashimoto thyroiditis. We collected follicular fluid from 61 patients, namely 38 women with thyroid autoantibody positivity and 23 women as negative controls, undergoing in vitro fertilization treatment. Follicular fluid samples were analyzed using metabolomics, and thyroid autoantibodies were measured. Fifteen metabolites with higher concentrations in the follicular fluid samples from Hashimoto thyroiditis were identified, comprising five possible affected pathways: the glycerophospholipid, arachidonic acid, linoleic acid, alpha-linolenic acid, and sphingolipid metabolism pathways. These pathways are known to regulate ovarian functions. In addition, antithyroglobulin antibody concentrations in both serum and follicular fluid were more than tenfold higher in women with Hashimoto thyroiditis than in controls. Our data showed that the metabolic profile of follicular fluid is altered in women with Hashimoto thyroiditis, suggesting a potential mechanistic explanation for the association of this disease with female infertility.

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.

ART in Latin America: the Latin American Registry, 2020.

RESEARCH QUESTION: What was the utilization, effectiveness and safety of assisted reproductive technology (ART) in Latin America during 2020? DESIGN: Retrospective collection of multinational data on ART performed by 188 institutions in 16 countries. RESULTS: Overall, 87,732 initiated cycles resulted in 12,778 deliveries and 14,582 births. The major contributors were Brazil (46.0%), Mexico (17.0%) and Argentina (16.8%). However, the highest utilization (cycles/million inhabitants) was Uruguay with 558, followed by Argentina with 490 and Panama with 425 cycles/million. Globally, women aged ≥40 years increased to 34% while women ≤34 dropped to 24.7%. After removing freeze-all cycles, the delivery rate per oocyte retrieval was 14.8% for intracytoplasmic sperm injection and 15.6% for IVF. Single-embryo transfer (SET) represented 38.3% of all fresh transfers, with delivery rate per transfer of 20.0%; this increased to 32.4% for elective SET (eSET) and 34.2% for blastocyst eSET, compared with blastocyst elective double embryo transfer (eDET) of 37.9%. However, multiple births increased from 1% in eSET to 30.5% in eDET. Perinatal mortality increased from 7.7‰ in singletons to 24.4‰ in twins and 64.0‰ in triplets. Frozen embryo transfer (FET) represented 66.6% of all transfers, with a delivery rate/transfer of 29.0%, significantly higher than 23.9% after fresh transfers at all ages (p<0.0001). Preimplantation genetic testing, reported in 8920 cycles, significantly improved delivery rate and decreased miscarriage rates at all ages (p≤0.041), including oocyte donation (p=0.002). Endometriosis was diagnosed in 28.3% of cases. The delivery rate in 5779 women after removal of peritoneal endometriosis was significantly better than tubal and endocrine factors in women aged 35-39 (p=0.0004) and women aged ≥40 (p=0.0353). CONCLUSIONS: Systematic collection and analysis of big data in a south-south cooperation model allow regional growth by implementing evidence-based reproductive decisions.

The management of infertility for primary care physicians.

To conduct this review of primary care, we looked for related papers in PubMed from the last 15 years. WHO's initial concept of Health defined a condition of physical, mental, and social well-being, nowadays extended to quality of life. Infertility or not being able to form a family fits perfectly into the definition. Primary care is responsible for mandatory discussions about fertility as part of a broader aspect regarding reproductive health issues. Having children is a decision taken by heterosexual couples, same sex couples, or single individuals. Understanding factors associated with infertility help guiding propedeutic. Although woman's age is one of the main factors to influence treatment success rates, multifactorial male factor may contribute to 50 percent. Infertility consultations should include partners, alleviating the accompanying stress and anxiety. Anamnesis must focus on duration of infertility, primary or secondary, sexual activity, and lifestyle habits such as smoking, alcohol consumption, diet, physical activity, use of licit and/or illicit drugs, and occupational risks. Previous treatments should be accessed. Management of infertility by primary care is mandatory, and patients requiring specialized treatments must not have their journey protracted. Strategies and couple-based interventions are essential to continuity of care and close follow-up should follow these patients.

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.

Obese women and in vitro fertilization: results.

OBJECTIVE: To evaluate the effect of female obesity on the results of In Vitro Fertilization (IVF) in six parameters: dose of gonadotropins required, number of oocytes retrieved and fertilization, pregnancy, miscarriage and live births rates. METHOD: Literature search in PUBMED articles in English between 2008 and 2013 using the following keywords: female, obesity and In Vitro Fertilization. 15 articles were selected for this work. RESULTS: From the total only two articles showed that female obesity does not alter the results of IVF. The remaining 13 came to the conclusion that obesity has a negative effect on some of the parameters evaluated. However, there was no consensus about its effect. CONCLUSION: Further studies are needed to clarify the real role of obesity in female patients undergoing IVF, but the weight loss prior to treatment should always be encouraged.

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.

Evaluation of the Effects of Platelet-Rich Plasma on Follicular and Endometrial Growth: A Literature Review.

Platelet-rich plasma (PRP) has been used in several areas of medicine due to its ability to promote tissue regeneration by growth factors and cytokines. This review addresses the use of PRP to rejuvenate ovarian follicles and increase the thickness of the endometrium to receive an embryo. PRP is obtained from the patient's own blood (autologous blood) - a fact that determines a lower chance of rejection reactions. Alpha granules of platelets provide and release supra physiological amounts of growth factors and cytokines, which provide a regenerative stimulus in tissues with low healing potential. In the ovary, PRP and its growth factors stimulate vascularization and recruitment of available primordial follicles that could no longer be otherwise stimulated. The rejuvenation of the ovary by PRP infusion aims to obtain new oocytes in ovaries with low numbers of follicles or low follicular reserve markers. In the preparation of the endometrium, PRP is used for its several growth factors that allow tissue proliferation and endometrial thickening, especially in cases of endometria that are difficult to prepare or that fail to reach an adequate minimum thickness (>7mm). To date, there are few studies of greater expression in the literature that support the use of PRP with the two purposes described above. Thus, although promising, the technique must still be validated by larger clinical trials.

Evaluation of follicular flushing with double lumen needle in patients undergoing assisted reproductive technology treatments.

OBJECTIVE: The purpose of this study was to investigate the possible impact of follicular flushing on the number of oocytes retrieved and oocytes in metaphase II in patients with poor ovarian response (POR) compared to direct aspiration. METHODS: This prospective, comparative, randomized single center study included 208 punctures of patients with POR, submitted to assisted reproduction technology (ART) treatments. Two groups were compared; one in which double lumen needles were used (Wallace DNS1733) for follicular flushing (n=105), and one in which single lumen needles were used (Wallace ONS1733) for direct aspiration (n=103), upon the observation of ≤ 5 follicles between 15-17 mm, ≤ 4 follicles with sizes greater than 18 mm on hCG day, and ≤ 7 recovered oocytes. RESULTS: There were no differences in age (39.07±3.88 vs. 38.11±3.43); weight (61.73±17.53 vs. 65.96±15.44); AMH (0.63±0.59 vs. 0.94±0.97); stimulation days (9.57±1.87 vs. 10.29±2.82); estradiol levels (788.94±670.82 vs. 940.16±694.69); progesterone (617.29±319.76 vs. 561.18±486.78); or number of follicles with sizes ≥18 mm (1.84±0.95 vs. 2.07±1.09). Although gonadotropin totals (1678.28±798.52 vs. 2080.45±852.36; p=0.0008), number of aspirated oocytes (3.00±2.11 vs. 3.69±2.20; p=0.02), and number of metaphase II oocytes (2.20±1.64 vs. 2.99±1.88; p=0.02) were significantly different, oocyte / follicle ratio ≥15 mm (0.93 vs. 0.98) and metaphase II oocytes / follicles ≥15 mm (0.68 vs. 0.79) were similar in both groups. The failure to capture was 16% vs. 9.8%. CONCLUSIONS: Considering that there was no difference in the oocyte per follicle ratio, follicular flushing did not increase the number of oocytes recovered from poor responders.

Psychological Intervention in the Oocyte Pick-up Room and Recovery Room in Assisted Reproduction: new listening accounts.

OBJECTIVE: This study seeks to identify the role and possible participation of a psychologist/psychoanalyst inside an Oocyte Pick-up Room and Recovery Room (OPR-RR) in an Assisted Reproduction clinic and its implications on patients and team. METHODS: Prospective study of psychological support during the procedures from September 2014 to December 2018. Most visits took place during oocyte retrievals, for either IVF/ICSI or gamete freezing. RESULTS: Of the 2,343 cases, the psychologist was present in 965 of them (41%), during oocyte retrievals, with available professionals in 59% of the times (722 cases). The embryo transfers (1,011) had psychological assistance in 20% of the time (218 cases). The intrauterine insemination cases were excluded for not happening in a surgical environment. The recovery room was identified as one of the spaces for welcoming and listening to anxieties, desires, projects, worries, fears, frustrations, joys and expectations for those who come to the clinic seeking the desire to gestate. The patients' talks, collected in observations transcribed from what was heard, with dates and types of procedures, were discussed with either the team or the assistant physician. The team stands positively in the presence of a psychologist/psychoanalyst, who brings new perceptions and the development of the whole art of listening, for all involved. CONCLUSION: The presence of a psychologist/psychoanalyst in the Oocyte Pick-up Room and the Recovery Room in an Assisted Reproduction clinic means an opportunity to listen to patients' emotions, providing well-being to patients and echoing in the teamwork relationships.

Bladder hematoma: a complication from an oocyte retrieval procedure.

INTRODUCTION: More than one million fertilization cycles are performed every year. The incidence of serious complications associated with transvaginal oocyte pick-up is low, but the procedure is not risk-free. Risks are inherent to procedures in which thin needles and sharp instruments are introduced into the vaginal wall and ovarian capsule to access the ovaries. CASE DESCRIPTION: A 45-year-old patient reported urinary discomfort and difficulty urinating after her second cycle, 12 hours after oocyte pick-up. She had visible hematuria with small blood clots. Transvaginal ultrasound examination performed 24 hours after pick-up showed a heterogeneous intravesical image suggestive of a clot; her bladder measured 23x19mm. She was afebrile and in good condition. The patient was managed conservatively and offered fluids. The clot was expelled within a matter of hours. This case of a bladder hematoma was the first in the 21 years of a clinic where all procedures are guided by ultrasonography with clear visualization of the tip of the needle throughout the 15-20 minutes of the procedure. Patients submitted to ultrasound-guided transvaginal oocyte pick-up procedures in IVF protocols must be informed of this rare potential complication.