OBJECTIVE: Controlled ovarian hyperstimulation (COH) has been reported to affect thyroid function; however, the impact of thyroid-stimulating hormone (TSH) levels during COH on embryo development and early reproductive outcomes has largely not been determined. Therefore, the aim of the present study was to investigate whether TSH levels are associated with COH and impact early reproductive outcomes in preconceptionally euthyroid women.
METHODS: This was a prospective cohort study. A total of 338 euthyroid women who underwent their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment using the gonadotropin releasing hormone agonist (GnRH-a) protocol were included. Samples were collected at different representative time points for TSH and estradiol measurements.
RESULTS: TSH levels significantly increased with the administration of Gn and maintained this tendency until the trigger day. Basal TSH levels increased along with basal estradiol levels and remained stable when estradiol levels were higher than 150 pmol/L. On the trigger day, TSH levels changed with increasing estradiol levels in the high-normal basal TSH group but not in the low TSH group. TSH did not impact clinical pregnancy or early pregnancy loss after adjusting for age, stage or number of embryos.
CONCLUSIONS: Serum TSH levels change significantly during COH and are associated with significant changes in estradiol levels. However, euthyroid women with high-normal TSH levels showed similar development potential for inseminated embryos and early reproductive outcomes compared to those with low TSH levels.

UNASSIGNED: To examine body weight change in women undergoing in vitro fertilization and embryo transfer (IVF-ET) using antagonist protocol after up to three treatment cycles.
UNASSIGNED: A prospective cohort study among IVF patients treated between 2018 and 2019. Each patient underwent weight measurement three times during the treatment cycle: before treatment, at the beginning of the hormonal stimulation, and at the completion of the cycle, on the day of the pregnancy test. Data were also analyzed according to the body mass index (BMI) groups for normal weight, overweight, and obese patients. Finally, weight changes were recorded following altogether 519 treatment cycles, 240, 131, and 148 cycles, for normal weight, overweight, and obese patients, respectively.
UNASSIGNED: The change in the patient\'s weight was clinically non-significant either during the waiting period or during gonadotropin administration, and overall, during the first, second, or third treatment cycles. The recorded mean total weight change of 0.26 ± 1.85, 0.4 ± 1.81, and 0.17 ± 1.7, after the first, second, or third treatment cycles, represent a change of 0.36%, 0.56%, and 0.23% of their initial weights, respectively. This change of less than 1% of the body weight falls short of the clinically significant weight gain of 5%-7%. Analyzing the data for the various BMI groups, the changes observed in body weight were under 1%, hence with no clinical significance.
UNASSIGNED: The findings of the study reject the myth that hormone therapy involves clinically significant weight gain, and this can lower the concerns of many patients who are candidates for treatment of assisted reproductive technology.

Cyclopropene hydrofunctionalization has been a promising strategy for accessing multi-substituted cyclopropanes; however, cyclopropene hydroalkylation remains underdeveloped. Herein, we report a low-valent CoH-catalyzed facial-selective cyclopropene hydroalkylation to access multi-substituted cyclopropanes. This reaction exhibits a broad substrate scope of alkyl halides and cyclopropenes and tolerates many functional groups. Moderate-to-good facial-selectivity is obtained without any directing groups. Mechanism studies provide evidence that alkyl radicals are generated from alkyl halides and irreversible CoH insertion is responsible for the facial-selectivity. Our preliminary exploration demonstrates that asymmetric cyclopropene hydroalkylation can be realized without conspicuous auxiliary groups.

BACKGROUND: Follitropin Delta (FD) is indicated exclusively for in-vitro fertilization however, being a gonadotropin it could be used for other purposes. A dosing algorithm exists for FD and IVF but is needed for intrauterine insemination (IUI) cycles. The objective of this study is to determine dosing for FD for the first controlled ovarian hyperstimulation (COH) cycle according to current stimulation guidelines.
RESULTS: A retrospective study of 157 subjects from a single university fertility center from January 2017 to March 2020, was performed. All patients stimulated with FD for IUI were included. The number of failed, normal, or overstimulation cycles was determined based on stimulating not more than 2 mature follicles. We then stratified the group based on the AFC, AMH, and body weight. Of 157 subjects, 49% stimulated correctly, 5.6% failed and 45.4% overstimulated. An analysis of the COH IUI cycles based on stratification and over or lack of stimulation per published guidelines found that women with a bodyweight < 80 kg or AMH ≥ 1.5 ng/ml or AFC ≥ 10 initially stimulate with FD 2.0 to 3.0mcg daily. For women with an AFC of 6-9 stimulate with Follitropin Delta 3.0mcg daily. For women with an AFC < 6 or serum AMH < 1.5 ng/ml stimulate with FD 3.0-4.0mcg daily. For women with body weight > 80 kg stimulate initially with daily with 4.0-6.0mcg FD.
CONCLUSIONS: Follitropin Delta can be used safely for controlled ovarian stimulation and insemination at doses easily dispensed by the current methods of delivery, within the current published guidelines for follicle development.

Objective: Several studies evaluated the relationship between estrogen receptor (ER) polymorphisms and the outcomes of controlled ovulation hyperstimulation (COH). However, the results remained obscure. The objective of this study was to perform a meta-analysis to investigate the links between ER polymorphisms and COH outcomes.Methods: Eligible studies were identified from the following electronic databases: PubMed, Embase and the Chinese CNKI till Nov. 2021. The odds ratio (OR) and 95% confidence intervals (CIs) for dichotomous data and the weighted mean difference (WMD) with 95% confidence intervals (CIs) for continuous variables were used to calculate correlations between ER polymorphisms and COH outcomes. Based on the inclusion and exclusion criteria, a total of thirteen papers were eventually enrolled in the current meta-analysis.Results: The following were the key findings of this meta-analysis: (1) PvuII polymorphism had a significant relationship with IVF pregnancy outcome in all models, except the recessive model(CC VS TT: OR, 5.51, 95% CI, 1.13,26.84; CC + CT VS TT: OR, 3.73, 95% CI, 1.21,11.57; CT VS TT: OR, 3.19, 95% CI, 1.11,9.16;C VS T: OR, 2.19, 95% CI, 1.15, 4.19), with large or extreme heterogeneity; (2) XbaI polymorphism had a significant association with IVF risk in heterozygous and dominant models(AG VS GG: OR, 0.27, 95% CI, 0.12,0.61; AAAG VS GG: OR, 0.27, 95% CI, 0.12,0.59), with no heterogeneity; (3) (TA)n polymorphism was linked with IVF risk in the homozygous and recessive models(LL VS SS:OR = 3.74, 95%CI = 1.53,9.12;LL VS LS + SS:OR = 2.75, 95%CI = 1.18, 6.38), with no heterogeneity; (4) for Alul polymorphism and its association with POR risk, significant relationship was observed in the recessive model(AA VS AG + GG:OR = 2.27, 95%CI = 1.46, 3.54), with no heterogeneity;(5) PvuII T/C mutation did not predict the follicle number, oocyte number, ratio of follicles to oocytes and the risk of IVF;(6) for XbaI polymorphism and pregnancy outcome of IVF, no significant association was observed under all models; and (7) RsaI polymorphism does not increase the risk of POR under all models.Conclusion: In summary, our meta-analysis found evidence supporting that PvuII polymorphism may serve as a marker in predicting pregnancy rate in IVF-ET, XbaI and (TA)n polymorphisms may be related with infertility, and Alul polymorphism may predict the poor ovarian response to COH. More well-designed investigations are warranted to corroborate these findings.

Microglia are the principal glial cells involved in the processes of immune inflammation within both retina and optic nerve, especially under the context of glaucomatous neuropathy. Considering the distinguishing role of retinal microglia in glaucoma and the lack of established protocol for microglia isolation from animal glaucoma model, the present study aimed to develop and validate a method with characteristics of both simplicity and efficiency for retinal microglia isolation from chronic ocular hypertensive (COH) rats. A Percoll gradient of various concentrations was used to separate microglia from whole retinal cells of the COH rats and control group. The finally isolated microglia were identified by CD11b and Iba-1 immunofluorescence staining, and the cell viability was determined by trypan blue staining. Additionally, the proportion of microglia in the whole retina cells was identified by flow cytometry. Results showed that the survival rates of isolated retinal microglia with the Percoll gradient method were 67.2 ± 4% and 67.6 ± 3% in control and COH groups, respectively. The proportion of the microglia population in the whole retinal cells was about 0.4-0.93%. To conclude, the present study confirmed that the application of Percoll gradient could effectively separate microglia from retinas of COH rats, which will probably enrich the tool kit for basic researchers of glaucoma specialty and help with scientific investigations.

UNASSIGNED: Gonadotrophin releasing hormone agonist (GnRH-a) is widely used for pituitary down-regulation and recruiting more follicles in assisted reproduction. However, no information is available on its value for patients with thin endometrial thickness.
UNASSIGNED: This was a retrospective cohort study of 302 patients with endometrium <8 mm undergoing fresh embryo transfer at a fertility center of a university hospital from January 2016 and December 2018. In 148 cycles of the GnRH-a prolonged protocol, one depot of 3.75 mg GnRH-a was injected on day 2 of the menstrual cycle, while in 154 cycles of the short GnRH-a long protocol, 0.1 mg of GnRH-a was injected daily from the mid-luteal phase. The live birth rate and clinical pregnancy rate were compared between the two groups. Other outcome measures included the implantation rate, miscarriage rate, and characteristics of stimulation procedures.
UNASSIGNED: Live birth rates and clinical pregnancy rates were significantly higher in the GnRH-a prolonged protocol group than in the other group (36.5% vs 20.8%, P=0.002; 43.9% vs 28.2%, P=0.006, respectively). The live birth rate was significantly increased in the prolonged protocol group (crude OR: 2.190, 95% CI: 1.311, 3.660; adjusted OR: 2.458, 95% CI: 1.430, 4.224) compared with that in the reference group. The implantation rate of the former group was also significantly higher than that of the latter group (35.4% vs 15.9%, P=0.000). There was no significant difference in miscarriage rates between the two protocols. In terms of stimulation procedures, the GnRH-a prolonged protocol group required significantly higher Gn time (10.9 vs 9.5 days, P=0.000) and Gn consumption (2625.0 vs 2047.5 IU, P=0.000) than the short GnRH-a long protocol group.
UNASSIGNED: The GnRH-a prolonged protocol in fresh embryo transfer cycles yielded better clinical outcomes of patients with thin endometrium than the short GnRH-a long protocol.

Objective: To examine whether the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist protocol may improve conventional IVF/intracytoplasmic sperm injection (ICSI) cycle in poor ovarian response (POR) patients. Design: Cohort historical, proof of concept study. Setting: Tertiary, University affiliated Medical Center. Patient(s): Thirty POR patients, defined according to the Bologna criteria, who underwent a subsequent Stop GnRH-agonist combined with multiple-dose GnRH-antagonist controlled ovarian hyperstimulation (COH) protocol, within 3 months of the previous failed conventional IVF/ICSI cycle, were included. For the purposes of this study, we eliminated a bias in this selection by including only \"genuine\" poor responder patients, defined as those who yielded up to 3 oocytes following COH with a minimal gonadotropin daily dose of 300 IU. Main Outcome Measure(s): Number of oocytes retrieved, number of top-quality embryos, COH variables. Result(s): The Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol revealed significantly higher numbers of follicles >13 mm on the day of hCG administration, higher numbers of oocytes retrieved, and top-quality embryos (TQE) with an acceptable clinical pregnancy rate (16.6%). Moreover, as expected, patients undergoing the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol required significantly higher doses and a longer duration of gonadotropins stimulation. Conclusion(s): The combined Stop GnRH-ag/GnRH-ant COH protocol is a valuable tool in the armamentarium for treating \"genuine\" poor ovarian responders. Further, large prospective studies are needed to elucidate its role in POR and to characterize the appropriate patients subgroup (before initiating ovarian stimulation) that may benefit from the combined Stop GnRH-ag/GnRH-ant COH protocol.

The infertile patients with aging ovaries-also sometimes referred to as impending premature ovarian insufficiency (POI), impending premature ovarian failure (POF), or poor ovarian responders (POR), constitute a significant and increasing bulk of the patients appealing to IVF/ART. Different causes have been cited in the literature, among the identified etiologies, including chromosomal and genetic etiology, metabolic, enzymatic, iatrogenic, toxic, autoimmune, and infectious causes. Although the most successful and ultimate treatment of POI/POF/POR patients is egg donation (ED), many, if not most, of these infertile women are reluctant to consent to ED upon the initial diagnostic interview, requesting alternative solutions despite the low odds for success. Despite anecdotal case reports, no unequivocal treatment proved to be successful for these patients in prospective randomized controlled trials. Nevertheless, the addition of growth hormone (GH) to ovarian stimulation in POR with GH deficiency may improve the results of controlled ovarian hyperstimulation (COH) and the IVF success. In patients with autoimmune etiology for POR/POI, the combination of glucocorticosteroids, pituitary-ovarian suppression, and COH may be successful in achieving the desired conception.

OBJECTIVE: While FMR1 premutation carriers (CGG 55-200) were shown to have reduced success with IVF treatment (lower oocyte yield), studies reporting on the association between the number of CGG repeats and patients\' response to controlled ovarian hyperstimulation (COH) are inconsistent. In the present study, we aim to explore whether the number of CGG repeats in women with premutation in FMR1 gene, undergoing COH for IVF, correlates with COH variables and whether the number of AGG interruptions may function as a \"protective factor\" by improving the ovarian response to COH.
METHODS: Retrospective study, in an academic IVF-PGD unit. Fifty-seven consecutive FMR1 premutation carriers who underwent 285 IVF treatment cycles were included. The numbers of CGG repeats and AGG interruptions were retrieved and correlated to the demographics and COH variables.
RESULTS: There were no significant association between the numbers of CGG or the AGG interruptions and the number of oocyte retrieved or the peak estradiol levels. The lack of association was also observed when including all the IVF treatment cycles or only the first or last IVF treatment cycle. Moreover, no associations were found between the number of CGG repeats or AGG interruptions and other COH variables, i.e., duration of stimulation, the total dose of gonadotropin used, or the number of top-quality embryos.
CONCLUSIONS: No associations were observed between the number of CGG repeats or AGG interruptions and any of the COH variables. Further studies are required to identify early biomarkers of POI to empower FMR1 premutation carriers with risk assessment tools to consider procedures such as fertility preservation.