2021 ◽  
Vol 116 (3) ◽  
pp. e309
Natchandra Manoharrao Chimote ◽  
Bindu N. Chimote
1997 ◽  
Vol 68 (5) ◽  
pp. 927-930 ◽  
Louis N. Weckstein ◽  
Arnold Jacobson ◽  
Donald Galen ◽  
Kim Hampton ◽  
Janine Hammel

2021 ◽  
Zizhen Guo ◽  
Wei Chen ◽  
Yuqing Wang ◽  
Ran Chu ◽  
Xinxin Xu ◽  

Abstract Background A sufficient endometrial thickness (EMT) is essential for successful pregnancy. For patients with a thin endometrium (EMT ≤7.5 mm on human chorionic gonadotropin [HCG] trigger day) in IVF, some studies have suggested freezing all embryos and preparing the endometrium in the subsequent frozen-thawed cycle, but not all patients can obtain a thicker endometrium during endometrial preparation in the frozen embryo transfer cycle than on HCG trigger day in the fresh embryo transfer cycle. This study aimed to investigate which characteristics of patients with a thin endometrium suggest the possibility of EMT >7.5 mm in the subsequent frozen cycle, and build up a prediction nomogram.Methods Data were collected from the university-based reproductive medical center between January 2013 and September 2019. Multivariable logistic regression was used to generate the final prediction model and construct the nomogram. Model performances were quantified by discrimination and calibration.Results The predictive variables that entered the final model were: hysteroscopic adhesiolysis history, PCOS status, application of clomiphene in the ovarian stimulation process, the ovarian stimulation protocol, and the endometrial preparation protocol. The receiver operating characteristic curve for the final model and validation cohort was 0.76 (95% confidence interval [CI]: 0.722–0.797) and 0.71 (95% CI: 0.66–0.76), respectively. Discrimination performed well in both the modeling and validation cohorts.Conclusion We conclude that in women with a thin endometrium (EMT ≤7.5 mm on HCG trigger day), the absence of a hysteroscopic adhesiolysis history, and the presence of PCOS, the application of clomiphene in the ovarian stimulation process, the application of a GnRH agonist short protocol, mild stimulation protocol, natural cycle protocol, and natural cycle for endometrial preparation are prognostic for an increased possibility of EMT >7.5 mm in the subsequent frozen cycle.

2020 ◽  
Vol 35 (11) ◽  
pp. 2598-2608
Alberto Vaiarelli ◽  
Danilo Cimadomo ◽  
Erminia Alviggi ◽  
Anna Sansone ◽  
Elisabetta Trabucco ◽  

Abstract STUDY QUESTION Are the reproductive outcomes (clinical, obstetric and perinatal) different between follicular phase stimulation (FPS)- and luteal phase stimulation (LPS)-derived euploid blastocysts? SUMMARY ANSWER No difference was observed between FPS- and LPS-derived euploid blastocysts after vitrified-warmed single embryo transfer (SET). WHAT IS KNOWN ALREADY Technical improvements in IVF allow the implementation non-conventional controlled ovarian stimulation (COS) protocols for oncologic and poor prognosis patients. One of these protocols begins LPS 5 days after FPS is ended (DuoStim). Although, several studies have reported similar embryological outcomes (e.g. fertilization, blastulation, euploidy) between FPS- and LPS-derived cohort of oocytes, information on the reproductive (clinical, obstetric and perinatal) outcomes of LPS-derived blastocysts is limited to small and retrospective studies. STUDY DESIGN, SIZE, DURATION Multicenter study conducted between October 2015 and March 2019 including all vitrified-warmed euploid single blastocyst transfers after DuoStim. Only first transfers of good quality blastocysts (≥BB according to Gardner and Schoolcraft’s classification) were included. If euploid blastocysts obtained after both FPS and LPS were available the embryo to transfer was chosen blindly. The primary outcome was the live birth rate (LBR) per vitrified-warmed single euploid blastocyst transfer in the two groups. To achieve 80% power (α = 0.05) to rule-out a 15% difference in the LBR, a total of 366 first transfers were required. Every other clinical, as well as obstetric and perinatal outcomes, were recorded. PARTICIPANTS/MATERIALS, SETTING, METHODS Throughout the study period, 827 patients concluded a DuoStim cycle and among them, 339 did not identify any transferable blastocyst, 145 had an euploid blastocyst after FPS, 186 after LPS and 157 after both FPS and LPS. Fifty transfers of poor quality euploid blastocysts were excluded and 49 patients did not undergo an embryo transfer during the study period. Thus, 389 patients had a vitrified-warmed SET of a good quality euploid blastocyst (182 after FPS and 207 after LPS). For 126 cases (32%) where both FPS- and LPS-derived good quality blastocysts were available, the embryo transferred was chosen blindly with a ‘True Random Number Generator’ function where ‘0’ stood for FPS-derived euploid blastocysts and ‘1’ for LPS-derived ones (n = 70 and 56, respectively) on the website All embryos were obtained with the same ovarian stimulation protocol in FPS and LPS (GnRH antagonist protocol with fixed dose of rec-FSH plus rec-LH and GnRH-agonist trigger), culture conditions (continuous culture in a humidified atmosphere with 37°C, 6% CO2 and 5% O2) and laboratory protocols (ICSI, trophectoderm biopsy in Day 5–7 without assisted hatching in Day 3, vitrification and comprehensive chromosome testing). The women whose embryos were included had similar age (FPS: 38.5 ± 3.1 and LPS: 38.5 ± 3.2 years), prevalence of male factor, antral follicle count, basal hormonal characteristics, main cause of infertility and previous reproductive history (i.e. previous live births, miscarriages and implantation failures) whether the embryo came from FPS or LPS. All transfers were conducted after warming in an artificial cycle. The blastocysts transferred after FPS and LPS were similar in terms of day of full-development and morphological quality. MAIN RESULTS AND THE ROLE OF CHANCE The positive pregnancy test rates for FPS- and LPS-derived euploid blastocysts were 57% and 62%, biochemical pregnancy loss rates were 10% and 8%, miscarriage rates were 15% and 14% and LBRs were 44% (n = 80/182, 95% CI 37–51%) and 49% (n = 102/207, 95% CI 42–56%; P = 0.3), respectively. The overall odds ratio for live birth (LPS vs FPS (reference)) adjusted for day of blastocyst development and quality, was 1.3, 95% CI 0.8–2.0, P = 0.2. Among patients with euploid blastocysts obtained following both FPS and LPS, the LBRs were also similar (53% (n = 37/70, 95% CI 41–65%) and 48% (n = 27/56, 95% CI 35–62%) respectively; P = 0.7). Gestational issues were experienced by 7.5% of pregnant women after FPS- and 10% of women following LPS-derived euploid single blastocyst transfer. Perinatal issues were reported in 5% and 0% of the FPS- and LPS-derived newborns, respectively. The gestational weeks and birthweight were similar in the two groups. A 5% pre-term delivery rate was reported in both groups. A low birthweight was registered in 2.5% and 5% of the newborns, while 4% and 7% showed high birthweight, in FPS- and LPS-derived euploid blastocyst, respectively. Encompassing the 81 FPS-derived newborns, a total of 9% were small and 11% large for gestational age. Among the 102 LPS-derived newborns, 8% were small and 6% large for gestational age. No significant difference was reported for all these comparisons. LIMITATIONS, REASONS FOR CAUTION The LPS-derived blastocysts were all obtained after FPS in a DuoStim protocol. Therefore, studies are required with LPS-only, late-FPS and random start approaches. The study is powered to assess differences in the LBR per embryo transfer, therefore obstetric and perinatal outcomes should be considered observational. Although prospective, the study was not registered. WIDER IMPLICATIONS OF THE FINDINGS This study represents a further backing of the safety of non-conventional COS protocols. Therefore, LPS after FPS (DuoStim protocol) is confirmed a feasible and efficient approach also from clinical, obstetric and perinatal perspectives, targeted at patients who need to reach the transfer of an euploid blastocyst in the shortest timeframe possible due to reasons such as cancer, advanced maternal age and/or reduced ovarian reserve and poor ovarian response. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER N/A.

Endocrinology ◽  
2011 ◽  
Vol 152 (1) ◽  
pp. 334-334
John M. Twigt ◽  
Fatima Hammiche ◽  
Kevin D. Sinclair ◽  
Nicole G. Beckers ◽  
Jenny A. Visser ◽  

Background: Folate is a methyl donor. Availability of folate affects DNA methylation profiles and thereby gene expression profiles. We investigated the effects of low-dose folic acid use (0.4 mg/d) on the ovarian response to mild and conventional ovarian stimulation in women. Methods: In a randomized trial among subfertile women, 24 and 26 subjects received conventional and mild ovarian stimulation, respectively. Blood samples were taken during the early follicular phase of the cycle prior to treatment and on the day of human chorionic gonadotropin administration for determination of serum total homocysteine, anti-Müllerian hormone (AMH), estradiol, and folate. Folic acid use was validated by questionnaire and serum folate levels. Preovulatory follicles were visualized, counted, and diameters recorded using transvaginal ultrasound. The relation between folic acid use and ovarian response was assessed using linear regression analysis. Results: Folic acid use modified the ovarian response to ovarian stimulation treatment. The estradiol response was higher in nonfolic acid users receiving conventional treatment [βinteraction = 0.52 (0.07–0.97); P = 0.03], and this effect was independent of serum AMH levels and the preovulatory follicle count. In the conventional treatment, the mean follicle number was also greater in nonusers compared with the users group (14.1 vs. 8.9, P = 0.03). Conclusion: Low-dose folic acid use attenuates follicular and endocrine responses to conventional stimulation, independent of AMH and follicle count. The nature of this observation suggests that the effect of folic acid is most prominent during early follicle development, affecting immature follicles. Deleterious effects of folate deficiency, like DNA hypomethylation and oxidative stress, can help to explain our observations.

2021 ◽  
Joy E. Chiu ◽  
Isaline Renard ◽  
Anasuya C. Pal ◽  
Pallavi Singh ◽  
Pratap Vydyam ◽  

AbstractTargeting conserved metabolic processes that are essential for viability of pathogens, such as Plasmodium and Babesia that cause blood-borne diseases, is an effective strategy to eliminate malaria and babesiosis infections with no recrudescence. One interesting target is the mitochondrial cytochrome bc1 complex, which could be inhibited by drugs such as endochin-like quinolones (ELQ) and atovaquone. We used the tick-transmitted and culturable blood-borne pathogen Babesia duncani to evaluate the structure-activity relationship, safety, efficacy and mode of action of ELQs. We identified a potent and highly selective ELQ prodrug (ELQ-502), which alone or in combination with atovaquone eliminates B. microti and B. duncani infections in vitro and in mouse models of parasitemia and lethal infection. The strong efficacy at low dose, excellent safety, bioavailability and long half-life of this experimental therapy makes it an ideal clinical candidate for the treatment of human infections caused by Babesia and its closely related apicomplexan parasites.

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