scholarly journals P–670 Urine estrone–3-glucuronide (E3G) assay: is there any place during ovarian stimulation for IVF cycles?

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
I Vladimirov ◽  
V Martin ◽  
T Desislava

Abstract Study question Could the urine estrone–3-glucuronide (E3G) assay be used efficiently to monitor a controlled ovarian hyperstimulation (COH) cycle, in comparison to a serum estradiol (E2) assay? Summary answer E3G testing provides an alternative to serum E2 assessment and a new “patient friendly” approach for COH monitoring. What is known already In many IVF clinics basic monitoring tools for controlled ovarian stimulation during IVF procedure are ultrasound measurements of follicle growth and hormone assessment of serum E2 levels. The monitoring can occur 4–6 times during stimulation, but repeated blood sampling causes patient stress. In contrast, E3G sampling, one of principal metabolites of estradiol in urine, is non-invasive and can be performed by the patients themselves and measured by fluorescent immunoassay. A correlation has been shown between concentrations of E2 present in plasma and concentrations of E3G in different phases of menstruation cycle. Study design, size, duration This is a pilot, prospective study, in a single IVF clinic. Twenty female participants were recruited November 2020 -January 2021, aged 25–43 years and BMI: 18–28kg/m2. Dynamic change of serum E2 and urine E3G at ovarian stimulation monitoring are being analyzed. Participants/materials, setting, methods Concurrent urine E3G and serum E2 values were collected from patients who provided between 2 and 4 samples on different days of their COH IVF cycle. Serum E2 values were assessed routinely, while E3G values were measured and validated using a fluorescent immunoassay Mira Fertility Plus® analyzer.Main results and the role of chance: The urine E3G of assay was validated for intra- and inter-assay variability with a coefficient of variation of < 20%. It was also validated for analytical and functional sensitivity and sample stability. Linear regression of serum E2 and E3G values of 56 early morning urine samples who had evaluated between Days 4 and 13 of menstruation cycle provided an R = 0,81. Urine E3G values also correlated to follicle growth. Patient survey results showed that urine sampling was the preferred method of analysis. Limitations, reasons for caution We have provided proof of principle that urine E3G measurement can be accurately carried out using fluorescent immunoassay technology during routine COH for IVF cycles. The patients’ study group has to be expanded in order to enable us to find the appropriate place of urine E3G assay in COH protocol. Wider implications of the findings: Urine E3G testing correlates well to serum E2 assessment in COH. Urine E3G assay provides an alternative to serum-based assessment. The ease of urine sampling allows a reduction in patient discomfort during venopuncture, costs, time, and infection risks in epidemics/pandemics, like COViD–19, and offers a patient-friendly approach to ovarian stimulation. Trial registration number NA

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Norbert Gleicher ◽  
Andrea Weghofer ◽  
Sarah K. Darmon ◽  
David H. Barad

AbstractPreviously anecdotally observed rebounds in follicle growth after interruption of exogenous gonadotropins in absolute non-responders were the impetus for here reported study. In a prospective cohort study, we investigated 49 consecutive patients, absolutely unresponsive to maximal exogenous gonadotropin stimulation, for a so-called rebound response to ovarian stimulation. A rebound response was defined as follicle growth following complete withdrawal of exogenous gonadotropin stimulation after complete failure to respond to maximal gonadotropin stimulation over up to 5–7 days. Median age of study patients was 40.5 ± 5.1 years (range 23–52). Women with and without rebound did not differ significantly (40.0 ± 6.0 vs. 41.0 ± 7.0 years, P = 0.41), with 24 (49.0%) recording a rebound and 25 (51.0%) not. Among the former, 21 (87.5%) reached retrieval of 1–3 oocytes and 15 (30.6%) reached embryo transfer. A successful rebound in almost half of prior non-responders was an unsuspected response rate, as was retrieval of 1–3 oocytes in over half of rebounding patients. Attempting rebounds may, thus, represent another incremental step in very poor prognosis patients before giving up on utilization of autologous oocytes. Here presented findings support further investigations into the underlying physiology leading to such an unexpectedly high rebound rate.


2020 ◽  
Author(s):  
Yujia Ma ◽  
Bo Sun ◽  
Linli Hu ◽  
Fang Wang ◽  
Ying-Pu Sun

Abstract Background: Although serum basal follicle stimulating hormone (FSH) is widely used to evaluate the ovarian response, the necessity of levels of serum FSH during the controlled ovarian hyperstimulation (COH) is controversy. When the ovarian response to COH is suboptimal due to the insufficient dose of FSH, which is often adjusted in subsequent treatment accordingly, we could detect serum FSH levels and considering that exogenous FSH is inadequate to optimal FSH threshold. We, therefore, aim to evaluate the association between the ovarian response and the difference value of serum FSH concentration in the first five days of ovarian stimulation. Methods: In this retrospective single-center study, patients were enrolled for first IVF/ICSI during the period from August 2015 to December 2017. The COH only included gonadotrophin-releasing hormone agonist (GnRH-a) protocols in which endogenous serum FSH values were suppressed, and stimulated with 150IU fixed-dose recombinant FSH (rFSH) during the first five days. Patients met all inclusion criteria were selected: age ≤ 40 years, body mass index (BMI) ≤ 32 kg/m2, regular menstruation cycle of 21-35 days and non-ovarian factor infertility. Groups were divided by the amount of oocytes collection as follows: (A) poor responders (n=27), (B) normal responders (n=638), (C) hyper responders (n=205). A multivariable logistic regression model was performed to evaluate the relationship between the ovarian response and difference value of serum FSH levels during the first five days of ovarian stimulation.Result(s): The difference value of serum FSH level (ΔFSH) between the sixth day and the first day during ovarian stimulation was measured as the primary outcome. Mean serum ΔFSH levels between groups B and C were 7.45 and 6.87, which had significant differences (p=0.0259). ΔFSH was stratified in quartiles as below: (a) ΔFSH≤5.16, (b) ΔFSH 5.16-7.11, (c) 7.11-9.09, (d) ΔFSH˃9.09. After adjusted by potential confounding factors, there was no relationship exists between ΔFSH levels and ovarian response.Conclusion(s): There is no relevance between the ovarian response and ΔFSH in the 150 IU fixed dose rFSH treatment protocol during COH. Serum FSH might not be used as an effective predictor for ovarian response and reproduction potential in IVF/ICSI clinical practice.


2018 ◽  
Vol 53 (8) ◽  
pp. 513-522 ◽  
Author(s):  
Spencer Stuart Haines Roberts ◽  
Wei-Peng Teo ◽  
Stuart Anthony Warmington

ObjectivesTo characterise the sleep of elite athletes and to identify factors associated with training and competition that negatively affect sleep.DesignPrognosis systematic review.Data sourcesThree databases (PubMed, SCOPUS and SPORTDiscus) were searched from inception to 26 February 2018.Eligibility criteria for selecting studiesIncluded studies objectively reported total sleep time (TST) and/or sleep efficiency (SE) in elite athletes. Studies were required to be observational or to include an observational trial.ResultsFifty-four studies were included. During training, many studies reported athletes were unable to achieve TST (n=23/41) and/or SE (n=16/37) recommendations. On the night of competition, most studies reported athletes were unable to achieve TST (n=14/18) and/or SE (n=10/16) recommendations. TST was shorter (60 min) the night of competition compared with previous nights. SE was lower (1%) the night of competition compared with the previous night. TST was shorter the night of night competition (start ≥18:00; 80 min) and day competition (20 min) compared with the previous night. SE was lower (3%–4%) the night of night competition but unchanged the night of day competition compared with previous nights. Early morning training (start <07:00), increases in training load (>25%), late night/early morning travel departure times, eastward air travel and altitude ascent impaired sleep.ConclusionAthletes were often unable to achieve sleep recommendations during training or competition periods. Sleep was impaired the night of competition compared with previous nights. Early morning training, increases in training load, travel departure times, jet lag and altitude can impair athletes’ sleep.PROSPERO registration numberCRD42017074367.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Yunakova ◽  
I Kostov ◽  
N Magunska ◽  
I Antonova

Abstract Study question To investigate the factors which are associated with higher number and share of atretic oocites (AO) such as quintative ovarian reserve, gonadotropin doses, age, BMI, smoking, pelvic surgery. Summary answer: There are convincing data that factors as advanced age, overweight, smoking and pelvic surgery are related to higher share of AO, while stimulation doses not. What is known already Atretic eggs are cells that have different deviations in morphology - dark or granular cytoplasm, cytoplasmic fragments, dark area of ​​the pellucid, large perivithelial space, abnormalities in shape and are usless. There is no consensus on the reasons for their formation. Studies demonstrate that combined estimation of the quantitative and qualitative reserve of the ovary is difficult, the transformation of primordial follicles into antral takes months in which the cohort of antral follicles and gametes changes. There are speculations of the likely negative impact of lifestyle factors t like smikong, obesity, age. Other blame higher doses of gonadotropins. Study design, size, duration This is a 3 year retrospective study on 2721 IVF/ICSI cycles of controlled ovarian hyperstimulation with long or antagonist protocols. The mean number and share of AO of all oocites retrieved were calculated in order to investigate there relation to factors like ovarian reserve, gonadotropin doses, age, BMI, smoking, history of pelvic surgery. Participants/materials, setting, methods: Depending on the factors investigated, the study groups were formed as follows: = ovarian reserve - &lt;5antral folicles (AF)(n = 307), 5–10AF(n = 994), &gt; 10AF(n = 584) = stimulation doses –1500E (n = 365),1500–3000Е(n = 790), 3000–4500(n = 264), &gt; 4500Е(n = 34) = age - ≤ 30(n = 391), 31–34(n = 467), 35–39(n = 679),≥ 40(n = 412) = BMI - &lt;18.5(n = 109), 18.5–24.9(n = 668), 24.9–30(n = 277), &gt;30(n = 111) = smoking - (n = 431), nonsmoking (n = 286) = pelvic surgery - (n = 572), without surgery (n = 630). Main results and the role of chance Regarding the ovarian reserve the mean number of AO rises significantly (Н=59.7, р&lt;0.0001) in paralel with the rise of all oocites retrieved, but the shre of AO stays same in each group (Н=0.39, р=0.828). As regard of the influence of doses of gonadotropins on the share of AO, there is no difference related to the increase of doses (Н=1.69; p = 0.640) - it is comparable,15–20%. The findings concerning age are interesting - the total number of eggs retrieved by age expectedly decreases but the share of AO is same between groups (Н=4.8, р=0.185), around 20%. At the same time in the group of women with only AO retrieved, t43,1% are above 40 years. Overweight and smoking are strongly related to the higher share of AO in obese and smoking women - (Н=11.4; р=0.010) and (U = 54 342; p = 0.005) respectively. In addition among women with only AO, 73,9% are smoking (c2 =5.26; р=0.022). Regarding the influence of pelvic surgery on quality of eggs, data shows higher share of AO among operated one is18% (U = 165815; p = 0.012), probably due to inflammatory processes in the pelvis. Limitations, reasons for caution It is possible same women to be prsent in different study groups. Wider implications of the findings: Increse of stimulation gonadotropins increse the number of eggs retrieved and respectively the chances for pregnancy without compromising the quality of eggs. An increase in the share of AO are related to age, overweight, smoking,pelvic surgery in in the pelvis. These findings suggest preventive measures to preserve women’s fertility potential. Trial registration number Not aplicable


2005 ◽  
Vol 10 (6) ◽  
pp. 721-728 ◽  
Author(s):  
Renato Fanchin ◽  
Daniel H Méndez Lozano ◽  
Luca M Schonäuer ◽  
João Sabino Cunha-Filho ◽  
René Frydman

2019 ◽  
Vol 35 (1) ◽  
pp. 70-80 ◽  
Author(s):  
Santiago Munné ◽  
Steven T Nakajima ◽  
Sam Najmabadi ◽  
Mark V Sauer ◽  
Marlane J Angle ◽  
...  

Abstract STUDY QUESTION After controlled ovarian stimulation (COS) and IUI, is it clinically feasible to recover in vivo conceived and matured human blastocysts by uterine lavage from fertile women for preimplantation genetic testing for aneuploidy (PGT-A) and compare their PGT-A and Gardner scale morphology scores with paired blastocysts from IVF control cycles? SUMMARY ANSWER In a consecutive series of 134 COS cycles using gonadotrophin stimulation followed by IUI, uterine lavage recovered 136 embryos in 42% (56/134) of study cycles, with comparable in vivo and in vitro euploidy rates but better morphology in in vivo embryos. WHAT IS KNOWN ALREADY In vivo developed embryos studied in animal models possess different characteristics compared to in vitro developed embryos of similar species. Such comparative studies between in vivo and in vitro human embryos have not been reported owing to lack of a reliable method to recover human embryos. STUDY DESIGN, SIZE, DURATION We performed a single-site, prospective controlled trial in women (n = 81) to evaluate the safety, efficacy and feasibility of a novel uterine lavage catheter and fluid recovery device. All lavages were performed in a private facility with a specialized fertility unit, from August 2017 to June 2018. Subjects were followed for 30 days post-lavage to monitor for clinical outcomes and delayed complications. In 20 lavage subjects, a single IVF cycle (control group) with the same ovarian stimulation protocol was performed for a comparison of in vivo to in vitro blastocysts. PARTICIPANTS/MATERIALS, SETTINGS, METHODS Women were stimulated with gonadotrophins for COS. The ovulation trigger was given when there were at least two dominant follicles ≥18 mm, followed by IUI of sperm. Uterine lavage occurred 4–6 days after the IUI. A subset of 20 women had a lavage cycle procedure followed by an IVF cycle (control IVF group). Recovered embryos were characterized morphologically, underwent trophectoderm (TE) biopsy, vitrified and stored in liquid nitrogen. Biopsies were analyzed using the next-generation sequencing technique. After lavage, GnRH antagonist injections were administered to induce menstruation. MAIN RESULTS AND THE ROLE OF CHANCE A total of 134 lavage cycles were performed in 81 women. Uterine lavage recovered 136 embryos in 56 (42%) cycles. At the time of cryopreservation, there were 40 (30%) multi-cell embryos and 96 (70%) blastocysts. Blastocysts were of good quality, with 74% (70/95) being Gardener grade 3BB or higher grade. Lavage blastocysts had significantly higher morphology scores than the control IVF embryos as determined by chi-square analysis (P &lt; 0.05). This is the first study to recover in vivo derived human blastocysts following ovarian stimulation for embryo genetic characterization. Recovered blastocysts showed rates of chromosome euploidy similar to the rates found in the control IVF embryos. In 11 cycles (8.2%), detectable levels of hCG were present 13 days after IUI, which regressed spontaneously in two cases and declined after an endometrial curettage in two cases. Persistent hCG levels were resolved after methotrexate in three cases and four cases received both curettage and methotrexate. LIMITATIONS, REASON FOR CAUTION The first objective was to evaluate the feasibility of uterine lavage following ovarian stimulation to recover blastocysts for analysis, and that goal was achieved. However, the uterine lavage system was not completely optimized in our earlier experience to levels that were achieved late in the clinical study and will be expected in clinical service. The frequency of chromosome abnormalities of in vivo and IVF control embryos was similar, but this was a small-size study. However, compared to larger historical datasets of in vitro embryos, the in vivo genetic results are within the range of high-quality in vitro embryos. WIDER IMPLICATIONS OF THE FINDINGS Uterine lavage offers a nonsurgical, minimally invasive strategy for recovery of embryos from fertile women who do not want or need IVF and who desire PGT, fertility preservation of embryos or reciprocal IVF for lesbian couples. From a research and potential clinical perspective, this technique provides a novel platform for the use of in vivo conceived human embryos as the ultimate benchmark standard for future and current ART methods. STUDY FUNDING/COMPETING INTEREST(S) Previvo Genetics, Inc., is the sole sponsor for the Punta Mita, Mexico, clinical study. S.M. performs consulting for CooperGenomics. J.E.B. and S.A.C. are co-inventors on issued patents and patents owned by Previvo and ownshares of Previvo. S.N. is a co-author on a non-provisional patent application owned by Previvo and holds stock options in Previvo. S.T.N. and M.J.A. report consulting fees from Previvo. S.T.N., S.M., M.V.S., M.J.A., C.N. and J.E.B. are members of the Previvo Scientific Advisory Board (SAB) and hold stock options in Previvo. J.E.B and S. M are members of the Previvo Board of Directors. A.N. and K.C. are employees of Previvo Genetics. L.V.M, T.M.M, J.L.R and S. S have no conflicts to disclose. TRIAL REGISTRATION NUMBER Protocol Registration and Results System (PRS) Trial Registration Number and Name: Punta Mita Study TD-2104: Clinical Trials NCT03426007.


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