Dataset Information

Ovarian Folliculogenesis and Uterine Endometrial Receptivity after Intermittent Vaginal Injection of Recombinant Human Follicle-Stimulating Hormone in Infertile Women Receiving In Vitro Fertilization and in Immature Female Rats.

ABSTRACT: The uterine first-pass effect occurs when drugs are delivered vaginally. However, the effect of vaginally administered recombinant human follicle-stimulating hormone (rhFSH) on ovarian folliculogenesis and endometrial receptivity is not well established. We aimed to compare the efficacy of rhFSH administered vaginally and abdominally in clinical in vitro fertilization (IVF) treatment, pharmacokinetic study, and animal study. In IVF treatment, the number of oocytes retrieved, endometrial thickness and uterine artery blood perfusion were not different between women who received the rhFSH either vaginally or abdominally. For serum pharmacokinetic parameters, significantly lower Tmax, clearance, and higher AUC and T1/2_elimination of rhFSH were observed in women who received rhFSH vaginally, but urine parameters were not different. Immature female rats that received daily abdominal or vaginal injections (1 IU twice daily for 4 days) or intermittent vaginal injections (4 IU every other day for two doses) of rhFSH had more total follicles than the control group. In addition, the serum progesterone and progesterone receptors in the local endometrium were significantly higher in the groups treated with intermittent abdominal or vaginal injection of rhFSH, compared with those who recieved daily injection. In summary, vaginal administration of rhFSH may provide an alternative treatment regimen in women receiving IVF.

SUBMITTER: Hsu CC

PROVIDER: S-EPMC8509306 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Ovarian Folliculogenesis and Uterine Endometrial Receptivity after Intermittent Vaginal Injection of Recombinant Human Follicle-Stimulating Hormone in Infertile Women Receiving In Vitro Fertilization and in Immature Female Rats.

Hsu Chao-Chin CC Hsu Leonard L Hsueh Yuan-Shuo YS Lin Chih-Ying CY Chang Hui Hua HH Hsu Chao-Tien CT

International journal of molecular sciences 20211005 19

The uterine first-pass effect occurs when drugs are delivered vaginally. However, the effect of vaginally administered recombinant human follicle-stimulating hormone (rhFSH) on ovarian folliculogenesis and endometrial receptivity is not well established. We aimed to compare the efficacy of rhFSH administered vaginally and abdominally in clinical in vitro fertilization (IVF) treatment, pharmacokinetic study, and animal study. In IVF treatment, the number of oocytes retrieved, endometrial thicknes ...[more]

PMID: 34639109

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Project description:To explore the association between uterine volume and in vitro fertilization (IVF) reproductive outcomes of infertile patients with adenomyosis, we performed a retrospective cohort study of infertile patients with adenomyosis who underwent IVF from January 2009 to December 2019 in our clinical center. Patients were divided into five groups according to the uterine volume before the IVF cycle. A line graph was drawn to demonstrate the linear trend of IVF reproductive outcomes with uterine volume. Univariate and multivariate analyses were used to explore the association between uterine volume of adenomyosis patients and IVF reproductive outcomes in first fresh embryo transfer (ET) cycle, first frozen-thawed embryo transfer (FET) cycle, and per ET cycle. Kaplan-Meier curves and Cox regression were conducted to evaluate the association between uterine volume and cumulative live birth. A total of 1155 infertile patients with adenomyosis were included. Clinical pregnancy rate showed no significant correlation with uterine volume in first fresh ET cycle, first FET cycle, and per ET cycle; miscarriage rate showed an upward trend with uterine volume increasement, in which the uterine volume turning point was 8 weeks of gestation; live birth rate showed a downward trend with turning point of 10 weeks of gestation. Subsequently, patients were divided into two groups (uterine volume ≤ 8 weeks of gestation vs. uterine volume > 8 weeks of gestation). Univariate and multivariate analyses showed that patients with a uterus larger than 8 weeks of gestation had a higher miscarriage rate and a lower live birth rate in all ET cycles. Kaplan-Meier curves and Cox regression demonstrated lower cumulative live birth rate in patients with a uterine volume larger than 8 weeks of gestation. IVF reproductive outcome gets worse as uterine volume increases in infertile patients with adenomyosis. Adenomyosis patients with a uterus larger than 8 weeks of gestation had a higher miscarriage rate and a lower live birth rate.

Project description:BackgroundFollicle stimulating hormone (FSH) has been routinely used for ovulation induction. Because of rapid clearance of the hormone, FSH is commonly administered by daily intramuscular or subcutaneous injections in in-vitro fertilization (IVF). To reduce the number of visits to the clinic, an intermittent vaginal injection of rhFSH every 3 days employing the concepts of mesotherapy and uterine first-pass effect was invented and has successfully been applied in women receiving IVF treatment. This study was designed to monitor the pharmacokinetic pattern of rhFSH administered vaginally.MethodsTwelve healthy women with regular ovulatory cycles were recruited. All volunteers received gonadotrophin-releasing hormone agonist to suppress pituitary function and were assigned to receive single dose recombinant human FSH (rhFSH, Puregon 300) either using conventional abdominal subcutaneous injection or vaginal subcutaneous injection in a randomized cross-over study. Serum samples were collected at pre- scheduled time intervals after injections of rhFSH to determine immunoreactive FSH levels. Pharmacokinetic parameters characterizing rate [maximal plasma concentrations (Cmax) and time of maximal plasma concentrations (tmax)] and extent [area under the plasma concentration-time curve (AUC) and clearance] of absorption of rhFSH were compared.ResultsVaginal injection of rhFSH was well tolerated and no drug-related adverse reaction was noted. Our analysis revealed that tmax was significantly earlier (mean 6.67 versus 13.33 hours) and Cmax was significantly higher (mean 17.77 versus 13.96 IU/L) in vaginal versus abdominal injections. The AUC(0-infinity) was 1640 versus 1134 IU hour/L in vaginal and abdominal injections, respectively. Smaller plasma elimination rate constant (0.011 versus 0.016 hour-1), longer mean residence time (106.58 versus 70.47 hours), and slower total body clearance (292.2 versus 400.1 mL/hour) were also found in vaginal injection.ConclusionThe vaginal injection mode elicited a rapid and highly extended absorption of rhFSH injected compared to conventional abdominal injection. These data indicate that the rate and extent of FSH absorption from the injection site can vary depending on the route of the FSH administration.

Dataset Information

Ovarian Folliculogenesis and Uterine Endometrial Receptivity after Intermittent Vaginal Injection of Recombinant Human Follicle-Stimulating Hormone in Infertile Women Receiving In Vitro Fertilization and in Immature Female Rats.

Publications

Ovarian Folliculogenesis and Uterine Endometrial Receptivity after Intermittent Vaginal Injection of Recombinant Human Follicle-Stimulating Hormone in Infertile Women Receiving In Vitro Fertilization and in Immature Female Rats.

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