Higher Basal Follicle-stimulating Hormone Research Articles

Follicle Stimulating Hormone (FSH) as a Predictor of Decreased Oocyte Yield in Patients with Normal Anti-Müllerian Hormone (AMH) and Antral Follicle Count (AFC).

The purpose of the current study was to determine the utility of early follicular phase follicle-stimulating hormone (FSH) testing in patients undergoing in vitro fertilization (IVF). This was a retrospective review of patients from 2012 to 2015 at Mayo Clinic in Rochester, Minnesota, USA. Included subjects had a normal anti-Müllerian hormone (AMH) of 1 to 9 ng/ml and antral follicle count (AFC) of 10 to 29. Patients were stratified by FSH level when associated estradiol was less than 50 ng/ml. In total, 225 patients were categorized into three groups: high FSH (FSH ≥10 IU/L; n= 36), normal FSH (>5 IU/L and <10 IU/L; n=170), and low FSH (FSH ≤5 IU/L; n= 19). ANOVA and multiple logistic regression were used for statistical comparisons and for evaluation of the relationships between variables; significance level was set at <0.05. There were no significant differences in demographics, IVF cycle type, or peak estradiol level between the groups. Patients with a high basal FSH level had a similar clinical pregnancy rate and live birth rate compared to controls and patients with low FSH. High FSH level was associated with decreased follicular development (17 versus 22; p<0.01), oocyte yield (15 versus 18; p=0.02), and embryo yield (8 versus 10; p=0.04) despite higher total doses of gonadotropins. Patients with normal AMH and AFC levels could be further stratified into lower responders and starting doses of medications can be adjusted based on high basal FSH levels. Therefore, it is suggested to counsel patients on pregnancy outcomes which seem to be quite similar regardless of the FSH level.

Nomogram to predict pregnancy outcomes of emergency oocyte freeze-thaw cycles.

Background:Existing clinical prediction models for in vitro fertilization are based on the fresh oocyte cycle, and there is no prediction model to evaluate the probability of successful thawing of cryopreserved mature oocytes. This research aims to identify and study the characteristics of pre-oocyte-retrieval patients that can affect the pregnancy outcomes of emergency oocyte freeze-thaw cycles.Methods:Data were collected from the Reproductive Center, Peking University Third Hospital of China. Multivariable logistic regression model was used to derive the nomogram. Nomogram model performance was assessed by examining the discrimination and calibration in the development and validation cohorts. Discriminatory ability was assessed using the area under the receiver operating characteristic curve (AUC), and calibration was assessed using the Hosmer–Lemeshow goodness-of-fit test and calibration plots.Results:The predictors in the model of “no transferable embryo cycles” are female age (odds ratio [OR] = 1.099, 95% confidence interval [CI] = 1.003–1.205, P = 0.0440), duration of infertility (OR = 1.140, 95% CI = 1.018–1.276, P = 0.0240), basal follicle-stimulating hormone (FSH) level (OR = 1.205, 95% CI = 1.051–1.382, P = 0.0084), basal estradiol (E2) level (OR = 1.006, 95% CI = 1.001–1.010, P = 0.0120), and sperm from microdissection testicular sperm extraction (MESA) (OR = 7.741, 95% CI = 2.905–20.632, P < 0.0010). Upon assessing predictive ability, the AUC for the “no transferable embryo cycles” model was 0.799 (95% CI: 0.722–0.875, P < 0.0010). The Hosmer–Lemeshow test (P = 0.7210) and calibration curve showed good calibration for the prediction of no transferable embryo cycles. The predictors in the cumulative live birth were the number of follicles on the day of human chorionic gonadotropin (hCG) administration (OR = 1.088, 95% CI = 1.030–1.149, P = 0.0020) and endometriosis (OR = 0.172, 95% CI = 0.035–0.853, P = 0.0310). The AUC for the “cumulative live birth” model was 0.724 (95% CI: 0.647–0.801, P < 0.0010). The Hosmer–Lemeshow test (P = 0.5620) and calibration curve showed good calibration for the prediction of cumulative live birth.Conclusions:The predictors in the final multivariate logistic regression models found to be significantly associated with poor pregnancy outcomes were increasing female age, duration of infertility, high basal FSH and E2 level, endometriosis, sperm from MESA, and low number of follicles with a diameter >10 mm on the day of hCG administration.

Effect of chronological age of patients with diminished ovarian reserve on in vitro fertilization outcome

The aim of this study was to evaluate the effect of chronological age on the in vitro fertilization (IVF) outcome in patients with diminished ovarian reserve (DOR). Four hundred and forty-nine women with DOR who underwent IVF cycles were enrolled in the study. There were only 296 patients who obtained available embryos. The patients with no available embryos had a significantly lower antral follicle count (AFC) and higher basal follicle-stimulating hormone (FSH) concentrations than those of women with available embryos, but chronological age in the two groups was comparable. However, patients aged >40 obtained a significantly lower ongoing pregnancy rate (OPR) than patients aged 35 − 40 or <35 (6.38% versus 26.15% versus 28.17%, respectively). Multivariate analysis also showed that chronological age was the only parameter associated with clinical results. It implied that patients with DOR still have reasonable chances of achieving a pregnancy, but their prognosis is significantly affected by chronological age. Impact statement What is already known on this subject? Diminished ovarian reserve DOR is a disappointing issue in reproductive medicine. Ovarian reserve, which represents ovarian biological age, is closely related to chronological age. However, ovarian biological age does not always match chronological age. Some studies suggest that biological age is more important than chronological age in predicting the outcome of in vitro fertilization (IVF). However, these conclusions are controversial. What do the results of this study add? We found DOR patients with no available embryos had significantly lower antral follicle count (AFC) and higher follicle-stimulating hormone (FSH) concentrations than that of patients with available embryos, but chronological age in the two groups was comparable. However, for patients with available embryos, chronological age is the only parameter associated with clinical results. For women aged >40 with DOR, chronological age was significantly negatively associated with clinical results. What are the implications of these findings for clinical practice and/or further research? Patients with DOR can obtain available embryos and still have a reasonable chance of becoming pregnant, but their prognosis is greatly affected by chronological age. Therefore, patients with DOR should seek medical help for pregnancy as soon as possible. When DOR patients over the age of 40 plan IVF treatment, the cost-effectiveness of healthcare should be considered.

Effect of Progestin-Primed Ovarian Stimulation Protocol in Infertile Women with Basal Follicle-Stimulating Hormone Levels ≥15 IU/L: A Retrospective Analysis

Objective: To evaluate the efficacy of progestin-primed ovarian stimulation (PPOS) protocol in infertile women with high basal follicle-stimulating hormone (FSH) levels ≥15 IU/L. Methods: Patients with high basal FSH levels ≥15 IU/L with autologous oocytes from September 2016 to March 2019 were reviewed. Either medroxyprogesterone acetate 4 mg/d or clomiphene citrate (CC) 50 mg/d was administered daily from day 3 to the trigger day. When serum FSH levels decreased to ≤15.0 IU/L, a low dose of human menopausal gonadotropin (hMG) 75/150 IU/d was administered to promote late follicular development. Results: Two hundred and twenty women were retrospectively analyzed in this study. Among them, 139 patients were administered with PPOS protocol as the study group, and 81 patients were administered with CC protocol as the control group. The numbers of received oocytes and viable embryos were higher in the study group than those in the control group (1.5 ± 1.2 vs. 1.2 ± 0.8 and 0.8 ± 0.8 vs. 0.5 ± 0.6, respectively, P < 0.05). However, hMG duration and dosage were significantly higher in the study group than those in the control group (4.2 ± 2.7 d vs. 1.1 ± 2.3 d and 609.1 ± 424.5 IU vs. 140.7 ± 231.3 IU, respectively, P < 0.01). Incidence of luteinizing hormone surge and cycle cancellation rate were lower in the study group than those in the control group with statistical difference (2.88% vs. 16.05% and 36.50% vs. 50.63%, respectively, P < 0.05). Conclusions: PPOS protocol can effectively downregulate the endogenous FSH levels. Compared with CC protocol, treatment with PPOS protocol in patients with high basal FSH levels ≥15 IU/L could receive more oocytes and more viable embryos.

Induced multiple follicular growth and ongoing twin pregnancy by IVF in a woman with premature menopause

Menopause, natural or premature, was long been considered to be incompatible with conception with the own eggs of the women affected. Here we describe a case of a 32-year-old woman with premature menopause, characterized by amenorrea, the absence of antral follicles in the ovaries, high basal follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and extremely low antimullerian hormone (AMH) levels. After preliminary treatment with contraceptive pill for two months, and an injection of recombinant human chorionic gonadotropin (HCG) to boost intrinsic androgen production, ovarian stimulation, using a customized protocol with a patient-tailored combination of recombinant FSH and LH, in addition to daily injections of growth hormone, resulted in the recovery of 3 metaphase II eggs after double triggering with recombinant HCG. After transfer of two embros, obtained by intracytoplasmic sperm injection, an ongoing twin clinical pregnancy was achieved. These data show that oocyte recovery, fertilization, embryo development and pregnancy can be achieved, with the use of a customized ovarian stimulation protocol, even in young women with clear signs of advanced premature menopause.

Depression and coping strategies of Chinese women undergoing in-vitro fertilization

ObjectivesTo explore the relationship between coping strategies and depression, and the risk factors of depression among Chinese women in infertile couples undergoing in-vitro fertilization (IVF). Study designTwo hundred and eighty-eight women undergoing IVF completed the Center for Epidemiologic Studies Short Depression Scale and the Brief COPE Inventory. Demographic data were collected, hormone levels were tested and oocyte numbers were counted. ResultsThe incidence of depression was 22.6%. The prevalence of depression was higher among women who had been married for >8 years, women who had been infertile for >6 years and women with a family income ≤3000 CNY/month. High basal follicle-stimulating hormone, oocyte number and denial score were associated with greater risk of depression. High oestradiol (basal and peak), and substance use and humour scores were associated with lower risk of depression. ConclusionMany women in infertile couples undergoing IVF have depression. Preventive interventions should be provided for women with risk factors of depression, such as long duration of marriage, long duration of infertility, low monthly family income, high basal follicle-stimulating hormone, low serum oestradiol, high oocyte number, and use of denial as a coping strategy.

Luteal phase support with decapeptyl improves pregnancy outcomes in intracytoplasmic sperm injection with higher basal follicle-stimulating hormone or lower mature oocytes

BackgroundThe role of midluteal phase gonadotropin-releasing hormone (GnRH) agonist had been an issue of debate. The aim of this retrospective study was to evaluate the effect of a mid-luteal phase GnRH agonist as an additional luteal phase support (LPS) in patients receiving intracytoplasmic sperm injection (ICSI). Additionally, we elucidate which subgroup would gain the most benefit from GnRH agonist as LPS. MethodsThe medical records were retrieved from January 2009 to January 2012 and a total of 348 patients receiving ICSI were included in this retrospective study. Among them, 240 patients met the inclusion criteria of patients aged ≤38 years, previous assisted reproductive technology (ART) cycles ≤ 2. There were 147 patients in the decapeptyl group who received GnRH agonist decapeptyl 6 days after ICSI as additional LPS and 93 patients in the control group. Subgroupings were done according to advanced age, the number of previous ART cycles, high basal follicle-stimulating hormone (FSH) level, and patients who had fewer mature oocytes retrieved. Live birth rates, clinical pregnancy rate (CPR), and implantation rate were the primary outcomes. ResultsLPS with decapeptyl led to a higher implantation rate (24.5% vs. 17.0%, p = 0.023), a higher CPR (49.0%, n = 72 vs. 33.3%, n = 31, p = 0.023) and a higher live birth rate (41.5%, n = 61 vs. 28.0%, n = 26, p = 0.039). In the subgroup analysis, decapeptyl improved the CPR of those patients with basal FSH >8 mIU/mL (50.0%, n = 15 vs. 8.3%, n = 1, p = 0.031) and also improved CPR (42.3%, n = 11 vs. 0%, n = 0, p = 0.017) and live birth rate (30.8%, n = 8 vs. 0%, n = 0, p = 0.035) of patients whose number of mature oocytes was three or fewer. ConclusionThis study demonstrated that administration of decapeptyl as additional luteal support can enhance ICSI clinical outcomes. Those patients with higher basal FSH level or fewer number of mature oocytes may obtain particularly significant benefit.

A preliminary study on reduced dose (33 or 25 μg) gonadotropin-releasing hormone agonist long protocol for multifollicular ovarian stimulation in patients with high basal serum follicle-stimulating hormone levels undergoing in vitro fertilization–embryo transfer

The aim of the present study was to evaluate the clinical efficacy of half-dose (50 μg) and further reduced dose (33 or 25 μg) gonadotropin-releasing hormone agonist (GnRH-a; triptorelin) long protocols for multifollicular ovarian stimulation (MFOS) for patients with high basal serum follicle-stimulating hormone (FSH) level undergoing in vitro fertilization and embryo transfer (IVF-ET). One hundred and two IVF-ET cycles performed in 84 infertile patients with high basal serum FSH (>10.0 mIU/ml) were included in this retrospective study. Study subjects were assigned to two groups: continuous half-dose GnRH-a long protocol (group A, n = 63) vs. further reduced dose GnRH-a long protocol (group B, n = 39) from half-dose at the start of GnRH-a to one-third or one-quarter dose after pituitary downregulation. Exogenous FSH or human menopausal gonadotropin was administered for MFOS in step-down mode, four or fewer embryos were transferred, and the outcomes of MFOS were compared between the two groups. Serum estradiol (E2) level on the day of human chorionic gonadotropin administration was significantly higher in group B (mean ± standard deviation (SD): 1318.3 ± 1120.4 vs. 2054.9 ± 1773.5 pg/ml, p = 0.015). The number of transferable and good-quality embryos was also significantly higher in group B (mean ± SD: 2.9 ± 1.7 vs. 3.7 ± 2.0, p = 0.027; 1.8 ± 1.4 vs. 2.7 ± 2.0, p = 0.020). No statistically significant difference in the outcomes was observed with respect to the dose of gonadotropins administered, the number of oocytes retrieved or the clinical pregnancy rate. In conclusion, GnRH-a long protocol with a reduced dose, tapered from the starting half-dose to a third or a quarter of the normal dose after pituitary suppression, may be beneficial for MFOS in IVF-ET patients with a high basal serum FSH level. A further prospective randomized controlled study on a larger scale is needed to confirm these findings.

Should women with poor prognostic factors for controlled ovarian hyperstimulation undergo in vitro fertilization (COH-IVF) using ganirelix?

Objective: The purpose of this study was to evaluate whether patients ≥38 years of age with a previous history of high basal follicle stimulating hormone (FSH) concentration or cancelled cycles due to low response benefit from COH-IVF using ganirelix.

High-dose ovarian stimulation in young patients with high basal follicle-stimulating hormone undergoing in-vitro fertilization.

High-dose ovarian stimulation in young patients with high basal follicle-stimulating hormone undergoing in-vitro fertilization.

Low pulse oxygen saturation in post-menopausal women at high altitude is related to a high serum testosterone/estradiol ratio

Objective: The present study was designed to determine if low pulse oxygen saturation ( Sp o 2) in post-menopausal women at high altitude was related to high serum testosterone/estradiol (T/E 2) ratio. Method: Studies were carried out in 191 women living in Cerro de Pasco, Peru (4340 m above sea level) and in 56 women living in Lima (150 m asl). Body weight, height, Sp o 2, hematocrit, serum follicle stimulating hormone (FSH), T and E 2 levels were measured in all women. Body mass index (BMI), menopausal status and serum T/E 2 ratio were calculated from data. Result: At high altitude, the values of Sp o 2, serum T, and serum E 2 were significantly lower in post-menopausal than in pre-menopausal women. Hematocrit, serum FSH levels, and serum T/E 2 ratios were significantly higher in post-menopausal women. Serum T and E 2 levels, T/E 2 ratio, Sp o 2, and hematocrit levels were not further changed with time after menopause. Women with Sp o 2<85% had lower serum E 2, a higher serum T/E 2 ratio, and higher hematocrit values than women with Sp o 2>90%. At high altitude, multiple regression analysis showed that low Sp o 2 was related to menopausal status (−2.6±0.83; β±S.E.; P<0.002) and not to chronological age (−0.06±0.04; P: NS). Further analysis showed that low Sp o 2 was related to high basal serum FSH levels and a high serum T/E 2 ratio in the presence of an interaction between FSH and T/E 2. Conclusion: Low values of Sp o 2 in women at high altitude were related to a high T/E 2 ratio.

Clinical usefulness of basal FSH as a prognostic factor in patients undergoing intracytoplasmic sperm injection.

To determine if basal serum follicle stimulating hormone (FSH) level could be a prognostic factor of the clinical outcome in intracytoplasmic sperm injection (ICSI) cycles in the couples with male factor infertility. From December 1995 to March 1998, total 118 patients underwent in vitro fertilization and embryo transfer (IVF-ET) with ICSI due to male factor infertility were included in this study. Patients were allocated to the low basal FSH group (< 8.5 mIU/ml) and the high basal FSH group (> or = 8.5 mIU/ml). The basal levels of FSH were measured in the 3rd day of menstrual cycle preceding ovarian stimulation cycle in total IVF cycles by immunoradiometric assay (IRMA). Statistical analysis was performed using Student's t-test, Fisher's exact test, and chi 2 test as appropriate. Statistical significance was defined as p < 0.05. The total dose of exogeneous gonadotropin required in the high basal FSH group was significantly higher than that in the low basal FSH group. The numbers of retrieved oocytes and oocytes with grade I, II were significantly higher in the low basal FSH group. The clinical pregnancy rate per cycle in the low basal FSH group (16.2%) was significantly higher than that in the high basal FSH group (4.0%). These results suggested that the basal serum FSH levels could be predictive of pregnancy outcome and the results of controlled ovarian hyperstimulation (COH) in ICSI cycles.

PERSISTENT ALTERED SPERMATOGENESIS IN LONG-TERM CHILDHOOD CANCER SURVIVORS

This study evaluated male gonadal function in long-term survivors of childhood cancer and assessed the suitability of offering sperm analysis to all those patients independently of the diagnosis and treatment received. A total of 43 survivors of acute lymphoblastic leukemia (21), acute myeloid leukemia (1), neuroblastoma (8), ganglioneuroblastoma (1), ganglioneuroma (2), Wilms' tumor (9), and mesoblastic nephroma (1) underwent sperm analysis at a mean age of 20.2 years, after a mean time off treatment of 13.6 years. Eight of the patients (19%) were azoospermic, 2 (5%) were severely oligo-asthenozoospermic, and only 16 (37%) were normozoospermic. A control group of healthy volunteers aged less than or equal to 30 years included no azoospermic subjects, 7% severely oligo-asthenozoospermic, and 67% normozoospermic. Comparisons were also made with patients treated at our Human Reproductive Unit aged less than or equal to 30 years (n = 373) whose percentages for the above parameters were 4, 9, and 42%, respectively. Cumulated cyclophosphamide dose and basal follicle-stimulating hormone (FSH) levels were identified as independent factors associated with azoospermia or severe oligo-asthenozoospermia. Azoospermic and severely oligo-asthenozoospermic survivors had significantly smaller mean testicular volume and higher basal FSH levels than the other survivors, but small testicles (sum of both testicular volume less than or equal to 20 mL) and/or abnormally high basal FSH (> 10 mIU/mL) were present in only half of the azoospermic survivors. Male long-term survivors of childhood cancer constitute a high-risk subpopulation for altered sperm analysis. It seems justified to offer sperm analysis to all long-term survivors.

Joint basal and pulsatile hypersecretory mechanisms drive the monotropic follicle-stimulating hormone (FSH) elevation in healthy older men: concurrent preservation of the orderliness of the FSH release process: a general clinical research center study.

To appraise the neuroendocrine mechanisms that underlie a selective (monotropic) elevation of serum FSH concentrations in healthy older men, we sampled blood in 11 young (ages 21-34) and 8 older men (ages 62-72) men every 2.5 min overnight. Serum FSH concentrations were quantitated in an automated, high-sensitivity, chemiluminescence-based assay. Rates of basal and pulsatile FSH secretion were estimated by deconvolution analysis, and the orderliness of the FSH release process via quantitated the approximate entropy statistic. Statistical analysis revealed that healthy older men manifest dual neuroendocrine hypersecretory mechanisims; specifically, a 2-fold increase in the basal (nonpulsatile) FSH secretion rate, and a concurrent 50% amplification of FSH secretory burst mass (and amplitude). The regularity or orderliness of ad seriatim FSH release is preserved in older individuals. We postulate that higher basal FSH secretion in older men is a consequence of reduced testosterone negative feedback, whereas amplified FSH secretory burst mass reflects net enhanced stimulation of gonadotrope cells by endogenous FSH secretagogues (e.g. GnRH and/or activin). The foregoing specific mechanisms driving heightened FSH secretion in older men contrast with the lower-amplitude pulsatility and more disorderly patterns of LH release in the same individuals. Thus, the present data illuminate an age-dependent disparity in the disruption of FSH neuroregulation in the aging male.

Endometrial evaluation is not predictive for in vitro fertilization treatment.

The main purpose of this study was to evaluate ovarian function by clomiphene citrate (CC) challenge test in a group of tubal infertile women and to study endometrial morphological maturation in the early luteal phase of CC-stimulated cycles as compared to in vitro fertilization (IVF) treatment outcome. Four women presented with strongly retarded, proliferative endometrium in the luteal phase. Of these, three presented with impaired ovarian function, high basal follicle-stimulating hormone, and high follicle-stimulating hormone levels after clomiphene stimulation on cycle day 10. In the remaining 30 women, showing an in-phase endometrium after CC stimulation, a comparison of six morphological characteristics did not reveal any significant differences between the 14 women who did become pregnant and the 16 who did not. No significant differences in endometrial thickness were observed between the groups. Significant differences were found when comparing estradiol and progesterone area under the curve during the luteal phase (P < 0.001 and P < 0.01, respectively) between those who did and those who did not become pregnant. Luteal endometrium morphology was not a sharp instrument to detect differences between women who did and women who did not become pregnant following IVF treatment, while ovarian function, as measured by hormonal markers, seemed to be a more reliable prognostic factor for IVF treatment outcome.

A protocol using a low dose of gonadotrophin-releasing hormone agonist might be the best protocol for patients with high follicle-stimulating hormone concentrations on day 3.

We studied 98 in-vitro fertilization (IVF) patients with a high basal follicle stimulating hormone (FSH; >6.5 IU/l) concentration on day 3 who were treated with a low dose gonadotrophin-releasing hormone agonist (GnRHa) protocol and who had received in the previous 6 months a long protocol with GnRHa in a depot formula. The evaluation was made using the previous IVF cycle of the same patient as a control. The mean +/- SD age of the patients was 34.1+/-4.2 years. The use of a low dose agonist protocol ended with significantly less ampoules (37.5 versus 46.1), a shorter duration of stimulation (10.7 versus 12.3 days), a higher oestradiol concentration on day 8 (1068 versus 495 pg/ml), a higher number of mature oocytes (5.9 versus 4.4) and a higher number of good quality embryos (3.3 versus 2.3). The cancellation rate was lower (11 versus 24%). A GnRHa low dose protocol may be the protocol of choice for patients with high FSH concentrations on day 3. Larger randomized studies are needed to confirm these data.