Vitamin D levels in couples undergoing In vitro Fertilization: Lack of Association with Embryo Quality or Pregnancy Rates.

OBJECTIVE: To investigate the potential impact of vitamin D serum levels of couples going through in vitro fertilization in terms of embryo quality and pregnancy rates. DESIGN: Retrospective cohort study SETTING: Fertipraxis, private human reproduction center on Rio de Janeiro, Brazil. SUBJECTS: 267 couples who underwent intracytoplasmic sperm injection between January 2017 and March 2019. EXPOSURE: The couples were categorized into four groups based on 25OH vitamin D levels measured at the beginning of the stimulation protocol: Group 1 with levels ≥ 30 ng/mL for both women and men; Group 2 with levels < 30 ng/mL for both; Group 3 with women < 30 ng/mL and men ≥ 30 ng/mL; and Group 4 with women ≥ 30 ng/mL and men < 30 ng/mL. MAIN OUTCOME MEASURES: We consider quantity and quality of embryos during the cleavage and blastocyst stages as primary outcomes. Correspondingly, clinical pregnancy rate was regarded as a secondary outcome. RESULTS: Our findings revealed no significant correlations between the studied VD groups and the evaluated outcomes. This includes quantity and quality of embryos during the cleavage and blastocyst stages, as well as clinical pregnancy rate. Primary analysis revealed a small but statistically significant difference in the duration of controlled ovarian stimulation between group 1 and group 2 (p=0.035; CI=0.07 - 3.04) and between group 1 and group 3 (p=0.040; CI=0.05 - 3.23). CONCLUSION: The present study found no correlation between the studied VD levels and quantity and quality of cleavage or blastocyst stage embryos, nor did it show any impact on clinical pregnancy rates. Further well designed, prospective studies are warranted to determine whether and how vitamin D affects reproductive outcomes.

Vaginal micronized progesterone on preventing luteinizing hormone untimely surge in ART cycles: A prospective proof-of-concept study.

OBJECTIVE: A new approach to evaluate whether Progestin-Primed Ovarian Stimulation with micronized vaginal progesterone was as effective as using dydrogesterone in suppress LH pulse surge in young women under stimulation in an oocyte donor programme. METHODS: This prospective study included 21 patients aged 19 to 32 years-old stimulated with Elonva® 150, associated or not with Menopur® or Merional® (75 or 150IU) since the beginning of the cycle, plus HMG 150-225IU after the 8th day or just HMG 150-300IU per day. Patients were placed in a PPOS protocol with micronized vaginal progesterone (MVP) 200 mg (Gynpro® Exeltis or Junno Farmoquimica) every 12 hours or dydrogesterone (Duphaston® Abbott) 10 mg every 8 hours from the start of stimulation until the day after the GnRH trigger with Triptorelin 0.2 mg (Gonapeptyl daily®). The primary endpoint was the prevention of untimely LH surge, and secondarily the number of 16 mm follicles, retrieved oocytes and metafase II. RESULTS: Fourteen oocyte donor patients were prescribed MVP while seven others received dydrogesterone (DYG).The gonadotropin protocols included 04 with Corifollitropin alfa 150 plus HMG since the beginning and complemented after the 7th day, and 17 times of just HMG. There was no diferences in the number of follicles >10≤15mm, ≥16mm or number of metafase II oocytes. There was no untimely LH surge on both groups and no OHSS was developed after the agonist trigger. CONCLUSIONS: Progestin-Primed Ovarian Stimulation with micronized vaginal progesterone seems to be a compelling choice for preventing premature ovulation without compromising oocyte quality in women undergoing ovarian stimulation.

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.

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.

Herlyn-Werner-Wunderlich syndrome: A fertility-sparing approach to a rare mullerian anomaly.

The Herlyn-Werner-Wunderlich syndrome (HWWS) is characterized by the triad of uterus didelphys, obstructed hemivagina, and renal agenesis. The typical clinical presentation involves chronic pelvic pain, dysmenorrhea, and palpable abdominal mass, related to hematocolpos/hematometra. It is a rare disease, with a challenging clinical and radiological diagnosis. Surgery is the definitive treatment. Complications such as endometriosis, infertility and chronic pelvic pain occur more frequently and severely when diagnosis and treatment are delayed. This is a case report of a twelve-year-old patient admitted to the Gynecology Department of the Federal University of Rio de Janeiro's General Hospital (HUCFF/UFRJ), in March 2021, with progressive symptoms of dysmenorrhea and abdominal distention due to palpable abdominal mass. She had a previous history of congenital solitary kidney. Magnetic Resonance Imaging (MRI) showed a double uterus with hematometra and hematocolpos on the left side, pelvic endometriosis and left renal agenesis. Conservative clinical treatment with inhibition of the hypothalamic-pituitary-ovarian (H-P-O) axis was initiated while a definitive surgical approach was being defined. In June 2022, the patient underwent left hemi-hysterectomy and salpingectomy, achieving full remission of symptoms. Given the rarity of this syndrome and its potential complications, our report aims to familiarize clinicians with it, mostly those who work with children and adolescents, so that more patients have access to early diagnosis and adequate treatment. Consequently, future fertility can be effectively preserved.

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.

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.

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.

Altered Umbilical Cord Blood Nutrient Levels, Placental Cell Turnover and Transporter Expression in Human Term Pregnancies Conceived by Intracytoplasmic Sperm Injection (ICSI).

Assisted reproductive technologies (ART) may increase risk for abnormal placental development, preterm delivery and low birthweight. We investigated placental morphology, transporter expression and paired maternal/umbilical fasting blood nutrient levels in human term pregnancies conceived naturally (n = 10) or by intracytoplasmic sperm injection (ICSI; n = 11). Maternal and umbilical vein blood from singleton term (>37 weeks) C-section pregnancies were assessed for levels of free amino acids, glucose, free fatty acids (FFA), cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low-density lipoprotein (VLDL) and triglycerides. We quantified placental expression of GLUT1 (glucose), SNAT2 (amino acids), P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) (drug) transporters, and placental morphology and pathology. Following ICSI, placental SNAT2 protein expression was downregulated and umbilical cord blood levels of citrulline were increased, while FFA levels were decreased at term (p < 0.05). Placental proliferation and apoptotic rates were increased in ICSI placentae (p < 0.05). No changes in maternal blood nutrient levels, placental GLUT1, P-gp and BCRP expression, or placental histopathology were observed. In term pregnancies, ICSI impairs placental SNAT2 transporter expression and cell turnover, and alters umbilical vein levels of specific nutrients without changing placental morphology. These may represent mechanisms through which ICSI impacts pregnancy outcomes and programs disease risk trajectories in offspring across the life course.

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.

Estradiol and Progesterone Levels are Related to Redox Status in the Follicular Fluid During in vitro Fertilization.

Studies have reported a possible association between the levels of oxidative stress biomarkers in follicular fluid (FF) and infertility treatment outcomes. FF analysis can provide important information about oocyte quality. This study aimed to evaluate the possible correlation between oxidative stress biomarker and intrafollicular hormone levels and clinical and laboratory parameters in women during controlled ovarian stimulation. These women were undergoing in vitro fertilization with intracytoplasmic sperm injection (ICSI).The FF samples were acquired from September 2012 to February 2014 from women undergoing private fertility treatment in Rio de Janeiro, Brazil. A total of 196 women who were undergoing ICSI and had different infertility diagnoses were recruited. The FF from each patient (average patient age of 36.3 ± 4.3 years) was collected following puncture of just one follicle with the largest diameter. After ruling out blood contamination by spectrophotometry, 163 patient samples were utilized in the study. In the FF, the progesterone levels were negatively correlated with (a) hydrogen peroxide scavenging capacity (HPSC) (r = -0.294, P < 0.0001), (b) total number of follicles (r = -0.246, P < 0.001) and (c) total number of oocytes punctured (r = -0.268, P = 0.0001). The concentration of serum estradiol exhibited a positive correlation with intrafollicular HPSC (r = 0.165, P = 0.037). Our data indicate that the FF levels of estradiol and progesterone are related to the FF redox status, which is closely associated with the number of oocytes obtained during ICSI procedures.

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.

Maternal obesity influences the endocrine cord blood profile of their offspring.

Objective To compare the endocrine cord blood characteristics of offspring from obese mothers with those of offspring from healthy controls. Methods Cross-sectional case control study. SETTING: University medical centers. PATIENT(S): Offspring from obese mothers (n = 41) and healthy controls (n = 31). INTERVENTION(S): Cord blood withdrawal from neonates. MAIN OUTCOME MEASURE(S): Cord blood total cholesterol (TC), triglycerides (TGs), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), blood glucose (GL) and insulin (Ins). Result(s) Fetal GL and TGs were reduced in the offspring of obese women when compared to those in the offspring of the controls. The mean cord blood GL level was 47.8 mg/dL standard deviation (SD 33.1) in the offspring of the obese group vs. 57.9 mg/dL (SD 12.5) in the offspring of the control group, and the mean cord blood TG level was 26.5 (SD 33.6) in the offspring of the obese group vs. 34.6 (SD 12.3) in the offspring of the control group. Maternal obesity was also associated with reduced levels of TC and HDL-C in the pregnant women. Conclusion The observed results suggest that GL and TGs in the cord blood of the offspring of obese mothers were significantly lower than those in the offspring of the control group.

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.

Vitamin D Receptor TaqI Polymorphism Is Associated With Reduced Follicle Number in Women Utilizing Assisted Reproductive Technologies.

PURPOSE: Calcitriol, or 1,25-hydroxycholecalciferol, is the active form of vitamin D. It binds and activates vitamin D receptor (VDR). Infertility and defective folliculogenesis have been observed in female vdr-knockout mice; however, whether VDR polymorphisms affect human ovarian responses to controlled ovarian stimulation (COS) remains unclear. We hypothesized that VDR polymorphisms are associated with infertility and COS responses. Thus, we evaluated the association between the TaqI, BsmI, and FokI VDR polymorphisms and ovarian responses in women undergoing COS. METHODS: In this study, we recruited a control group (n = 121) comprising volunteers with a history of natural conception and a second group of women undergoing COS (n = 70). TaqI, BsmI, and FokI genotyping was performed via restriction fragment length polymorphism analysis or TaqMan qPCR and Sanger sequencing. Intrafollicular 25(OH)D contents were measured in follicular fluid collected from COS patients during oocyte retrieval. Ovarian response parameters were obtained from patient medical records. RESULTS: There were no significant differences in the genotype frequencies of VDR polymorphisms (TaqI, BsmI and FokI) between the control and COS groups. However, the allele frequency of TaqI (C allele) was significantly lower in the COS group than in the control group (p = 0.02). Follicle number but not oocyte number was lower in patients with TaqI polymorphic (TC/CC) genotypes (p = 0.03). Importantly, the ratio between the number of follicles retrieved and intrafollicular estradiol concentrations was higher in patients with the TC/CC TaqI genotypes (p < 0.02). CONCLUSION: We identified an association between the VDR TaqI polymorphism and reduced follicle number in women undergoing COS, suggesting that VDR signaling affects the ovarian response to stimulation via unknown mechanisms.