Higher Basal FSH Research Articles

Basal FSH values are positively associated with aneuploidy incidence in pre-advanced maternal age (AMA) but not in AMA patients.

To assess the impact of maternal age on the association between maternal basal FSH and aneuploidy. A retrospective study including data from 1749 blastocysts diagnosed as euploid or aneuploid by PGT-A (preimplantation genetic testing for aneuploidy). Aneuploidy incidence was compared between embryos from mothers with high vs. low basal FSH levels (above and below the group median, respectively) in total, pre-AMA (advanced maternal age; < 35years, 198 embryos) and AMA (≥ 35years, 1551 embryos) patient groups, separately. To control for the interference of potentially confounding variables, the association between aneuploidy and high basal FSH levels was assessed by multivariate logistic analysis in overall, pre-AMA and AMA patient groups. Overall, aneuploidy rate was 9% higher (p = 0.02) in embryos from patients with high basal FSH (63.7%) compared to those with low basal FSH (58.4%). In the pre-AMA subgroup, aneuploidy incidence was 35% higher (p = 0.04) in embryos from patients with high basal FSH (53.5%) compared to those with low basal FSH (39.4%). Differently, aneuploidy occurrence did not vary between embryos from AMA patients with low (61.0%) and high (64.8%) basal FSH (p = 0.12). The multivariate analysis revealed that, in pre-AMA embryos, the association between aneuploidy occurrence and high basal FSH is independent of potential confounding variables (p = 0.04). Maternal basal FSH values are associated with embryo aneuploidy in pre-AMA but not in AMA patients. The present findings suggest that basal FSH is a useful parameter to assess aneuploidy risk in pre-AMA patients and reinforce the hypothesis that excessive FSH signalling can predispose to oocyte meiotic errors.

Treatment of D-galactose-induced rat polycystic ovarian condition using Lepidium sativum and secondary antibodies.

There is still much to be discovered regarding the etiopathogenesis and management of polycystic ovarian syndrome (PCOS). Four groups of female Wister-Albino rats were established, each with a normal estrous cycle: control, D ( + ) galactose (D-galactose), Lepidium sativum (L. sativum), and prepared secondary antibody (Ab2). Serum samples were collected, and histopathological examination was performed on ovaries and spleen tissues. Immunoreactive anti-ovarian antibody (AOA) quantities were determined using a modified antigen-based ELISA procedure. ELISA assay kits were used to quantify FSH, LH, and estradiol 17 β concentrations. The study found that AOA concentration in undiluted samples was significantly higher in the second and fourth weeks after PCOS induction by D-galactose (p < 0.001). However, antibody index% and titer elevated in the D-galactose group. L. sativum's late efficacy was observed in the fourth week, while the concentration of undiluted samples in the D-galactose + Ab2 group lowered (p < 0.001). Higher basal FSH and LH levels and lower estrogen levels are associated with PCOS development. L. sativum's immunomodulatory properties may contribute to this association. Estradiol-17ß concentrations increased in D-galactose + L. sativum and D-galactose + Ab2 groups, respectively. Careful extrapolation of experimental models is crucial for clinical applications, as technical advancements make Ab2 production easier. Further study is needed to fully understand its potential in immunotherapy.

Prevalence and characteristics of thelarche variant.

Girls with early thelarche may show an intermediate clinical picture between isolated premature thelarche (PT) and central precocious puberty (CPP), defined as "thelarche variant" (TV), characterized by an FSH-predominant response, although a univocal definition is lacking. Retrospective analysis on 91 girls with early thelarche (<8 years) and advanced bone age and/or accelerated growth who underwent 104 LHRH tests. Patients were classified into CPP (LH peak ≥5 IU/L; n = 28, 31%), TV (FSH peak ≥20 IU/L, LH peak <5 IU/L; n = 15, 16%), or PT (FSH peak <20 IU/L and LH peak <5 IU/L; n = 48, 53%). TV patients were younger (5.51 years) and with less advanced bone age (+0.8 years). They had higher basal and peak FSH (2.5 and 26.6 IU/L) and lower basal and peak LH/FSH ratios (0.08 and 0.11). The prevalence of presence of ovarian follicles >5 mm in TV (42%) was similar to CPP but significantly higher than PT, whereas maximum ovarian volume was smaller in TV (1.0 cm3). At the last follow-up visit (available in 60% of the cases), 44% of TV developed CPP compared with 14% of PT (p = 0.04). At first evaluation, those who progressed to CPP had a higher basal FSH (3.2 IU/L), lower LH/FSH ratio (0.07), and a higher peak LH (4.1 IU/L) compared with those who did not progress to CPP (basal FSH 1.9 IU/L, p < 0.01; basal LH/FSH ratio 0.12, p < 0.01; peak LH 2.8 IU/L, p = 0.02). Using laboratory parameters only as a definition, we identified the clinical, laboratory, and imaging features of TV: these girls showed less advanced bone age and FSH predominance also at baseline, with smaller ovaries but with follicles >5 mm. Almost half of girls initially diagnosed as TV developed CPP at last follow-up visit, and these girls had higher baseline FSH, lower baseline LH/FSH ratio, and higher peak LH at first evaluation. Therefore, TV may represent a "precocious prepuberty" in which the FSH predominance may initially limit the progression into proper puberty, but it may eventually trigger full puberty (even CPP, depending on the girls' age).

O-206 The impact of oocyte central granularity (CG) on the outcomes of ICSI cycles: live birth achievement is only compromised if CG-derived embryos are transferred

Abstract Study question Does oocyte central granularity (CG) compromise post-ICSI live birth achievement? Are morphologically normal oocytes obtained from CG cycles also affected? Summary answer Oocytes with CG, but not morphologically normal oocytes obtained from cycles providing CG oocytes, present lower competence to achieve a live birth. What is known already Ooplasm central granularity (CG) is associated with alterations in the actin cytoskeleton and meiotic spindle potentially affecting meiotic accuracy, fertilisation dynamics and embryo development. We have recently reported lower fertilisation rates and slower morphokinetics associated with CG. However, to clarify whether CG does affect oocyte developmental competence and if it is associated with endocrine alterations that may also impinge on the performance of morphologically normal oocytes obtained in the same cycle, adequately powered studies assessing the clinical outcomes of cycles transferring embryos derived from CG oocytes or from their morphologically normal companions are needed. Study design, size, duration Retrospective analysis including 866 control ICSI cycles/patients providing only morphologically normal oocytes (NO) and 211 CG cycles/patients providing NO and CG oocytes, from July 2014 to August 2021. Clinical outcomes were compared (1) between cycles providing CG oocytes (CG) or not (Control 1), and (2) among cycles achieving a fresh transfer in which only NO were obtained (Control-T), CG oocytes were obtained but NO-derived embryos were transferred (NOT), and CG-derived embryos were transferred (CGT). Participants/materials, setting, methods Patients undergoing their first ICSI cycle (n = 866; Control) or their first ICSI cycle providing CG oocytes (n = 211; Treatment-groups) were included. Cycle characteristics and outcomes were compared using the Fisher’s exact test and the Wilcoxon sum rank test. Multivariate analyses were performed to assess the potential interference of maternal age, infertility cause, number of embryos transferred and day of embryo transfer on the relationship between CG and live birth. Main results and the role of chance Patients providing CG oocytes (n = 211) presented higher maternal age (37.6± 4.5 vs. 36.5± 4.3; p= p &amp;lt; 0.001), higher basal FSH (8.5± 3.8 vs. 7.9± 4.1 IU/L; p = 0.03), lower AMH (2.2± 2.2 vs. 3.2± 3.5 ng/mL; p &amp;lt; 0.001), higher incidence of ovarian infertility (17.5% vs. 4.9%; p &amp;lt; 0.001) and higher FSH total dose (2255.3± 866.4 vs. 1825.6± 752.3 IU; p &amp;lt; 0.0001), compared to controls (n = 866). Implantation, abortion and live birth rates did not differ between cycles providing (CG) or not (Control) CG oocytes (22.7% vs. 24.9%, 17.1% vs. 27.7%, 25.8% vs. 22.9%, respectively). Nevertheless, implantation and live birth rates were lower in cycles in which CG-derived embryos were transferred (CGT; n = 87) compared to cycles in which CG oocytes were obtained but only NO-derived embryos were transferred (NOT; n = 57), or to cycles in which CG oocytes were not obtained (Control-T; n = 595). Implantation rates were 11.4%, 30.9% and 24.9%, while live birth rates were 10.5%, 30.2% and 22.9% for CGT, NOT and Control-T, respectively (p &amp;lt; 0.001 for implantation rates in CGT vs. NOT and CGT vs. Control-T; p &amp;lt; 0.04 for live birth rates in CGT vs. NOT and CGT vs. Control-T). No significant differences were observed between NOT and Control-T. Limitations, reasons for caution Our study is subjected to the limitations of a retrospective analysis and thus the data may be affected by other variables that were not controlled for. Moreover, the intrinsic difficulty in obtaining a higher number of cycles in which only CG-derived embryos are transferred, limits the power of the analysis. Wider implications of the findings Our findings shed light on a still unsolved question in ICSI practice. The present data indicate that CG is associated with markedly reduced oocyte developmental competence, while the presence of CG oocytes in a cycle does not affect the quality of the companion normal oocytes. Trial registration number not applicable

P–152 Morphokinetic and maternal profiles of embryos derived from centrally granulated oocytes vary with their ability to implant

Abstract Study question Does oocyte central granularity (CG) impact embryo morphokinetics and does this change with embryo implantation ability and maternal profile? Summary answer Oocyte CG slows fertilization and cleavage morphokinetics in overall derived embryos, but not in those capable to implant, an ability associated with lower maternal age. What is known already Oocyte morphology is easily accessible after pre-ICSI oocyte denudation, but the implications of morphological alterations for oocyte developmental competence are not entirely known. The presence of a centrally located granular area in the ooplasm was previously associated with alterations in the actin cytoskeleton and meiotic spindle, both potentially affecting meiosis completion, fertilization dynamics and embryo mitotic divisions. In fact, we have recently reported lower fertilization rates and delayed pronuclei fading and first cleavage associated with the presence of CG in oocytes subjected to ICSI. Study design, size, duration Retrospective analysis including 1378 control ICSI cycles providing only morphologically normal oocytes (1225 patients) and 220 CG cycles (201 patients) providing normal and CG oocytes, from July 2014 to March 2020. Morphokinetic parameters were compared between embryos from control and CG oocytes, as well as among embryos from control oocytes reaching implantation (C-I) and embryos from CG oocytes achieving (CG-I) or not (CG-NI) implantation. Maternal profiles were compared between CG-I and CG-NI. Participants/materials, setting, methods Oocytes were recovered from patients after controlled ovarian stimulation and ovum pick-up. Following ICSI, embryo culture was performed in a time-lapse incubator with annotation of time of pronuclei fading (tPNf) and cleavage times t2, t3, t4, t5 and t8. Morphokinetic data were retrospectively coupled with implantation outcomes of single transfers and of double transfers achieving double or no implantation. Differences were assessed with Chi-square and Kruskal Wallis tests. Main results and the role of chance Patients providing CG oocytes (n = 201) presented higher maternal age (37.4 ± 4.4 vs. 36.7 ± 4.3; p = 0.005), higher basal FSH (8.52 ± 3.7 vs. 7.62 ± 2.8 IU/L; p = 0.002) and lower AMH levels (2.2 ± 2.2 vs. 2.9 ± 3.1 ng/mL; p &amp;lt; 0.001) compared to control patients (n = 1225). Morphokinetic parameters from tPNf to t4 were faster in embryos derived from oocytes with normal morphology (control; n = 6947) compared to embryos derived from CG oocytes (n = 382; tPNf: 24.0 ± 3.8 vs. 24.6 ± 3.6; t2: 27.0 ± 4.3 vs. 27.6 ± 4.1; t3: 37.0 ± 5.7 vs. 37.4 ± 5.7; t4: 39.4 ± 6.4 vs. 40.1 ± 6.2 hours; p &amp;lt; 0.05). In addition, CG-NI (n = 103) embryos were slower than CG-I (n = 13) and C-I (n = 226) embryos for tPNf, t2, t3, t4 and t8 (p &amp;lt; 0.05), while CG-I did not differ from C-I embryos (p &amp;gt; 0.05; tPNf: 22.4 ± 2.6 vs. 22.0 ± 2.5; t2: 24.9 ± 2.7 vs. 24.6 ± 2.8; t3: 36.0 ± 3.5 vs. 35.4 ± 3.0; t4: 36.7 ± 3.5 vs. 36.7 ± 3.6 hours, for C-I and CG-I, respectively). Finally, patients providing CG-I embryos (n = 10) were younger than those providing CG-NI embryos (n = 65; 31.3 ± 4.6 vs. 38.0 ± 3.9; p &amp;lt; 0.05). Limitations, reasons for caution Our study is subjected to the intrinsic limitations of a retrospective analysis, the results presented could have been affected by variables that are uncontrolled for. Other studies are necessary to assess the impact of CG on clinical outcomes. Wider implications of the findings: The findings indicate that early developmental morphokinetics and maternal age constitute valid parameters for the decision of whether to transfer CG-derived embryos, as well as for the transfer prognosis. Trial registration number Not applicable

Correlation between Elevated Serum Progesterone in the Day of Hcg Injection, Metaphase II Oocytes and Their Impact on The Success of ICSI

Objective: In this study we tried to understand the effect of progesterone level at the time of ovulationtrigger on intracytoplasmic sperm injection (ICSI) outcome. We expected identifying cut off values forserum progesterone level the day of hCG injection (P-hCG) & P-hCG per mature oocyte ratio (P-hCG /MII), as predictive tests of ICSI success. Methods: 200 women 18-40 years old and attending IVF unitof Kasr el Aini hospital for management of infertility were included in the study. They were scheduled forICSI after controlled ovarian induction with GnRH- agonist protocol. Inclusion criteria were tubal factorof infertility, unexplained infertility, polycystic ovarian syndrome and BMI ? 30 kg/m2. Exclusion criteriawere severe male factor infertility, hyperprolactinemic patients, high basal FSH > 11 IU/L, frozen embryotransfer cycles, uterine anomalies or synechia. Primary outcome parameter included correlation of serumprogesterone on day HCG administration, number of MII oocytes and calculated progesterone/ MII oocyteratio with success of ICSI.Results: 193cases underwent embryo transfer, 7cases cancelled. Clinical pregnancy was reported in 52(27.9%) cases. Higher P-hCG was observed in cases who didn’t get pregnant compared to those who gotpregnant (p= 0.01) with cut off value of 1 ng/ml correlated well with the clinical pregnancy rate after ICSIwith 61% sensitivity and 59% specificity (p=0.004). A significantly lower P-hCG/MII ratio was found inthe pregnant women group compared to that found in the non-pregnant group (p=0.001) and cut off valueof 0.18 correlated best with clinical pregnancy after ICSI with sensitivity 70.5% and specificity 61.2%(p<0.001). Conclusion : We demonstrated negative correlation between P-hCG and P-hCG/MII andclinical pregnancy rate after ICSI.

Estrogens in Human Male Gonadotropin Secretion and Testicular Physiology From Infancy to Late Puberty.

Several reports in humans as well as transgenic mouse models have shown that estrogens play an important role in male reproduction and fertility. Estrogen receptor alpha (ERα) and beta (ERβ) are expressed in different male tissues including the brain. The estradiol-binding protein GPER1 also mediates estrogen action in target tissues. In human testes a minimal ERα expression during prepuberty along with a marked pubertal up-regulation in germ cells has been reported. ERβ expression was detected mostly in spermatogonia, primary spermatocytes, and immature spermatids. In Sertoli cells ERβ expression increases with age. The aromatase enzyme (cP450arom), which converts androgens to estrogens, is widely expressed in human tissues (including gonads and hypothalamus), even during fetal life, suggesting that estrogens are also involved in human fetal physiology. Moreover, cP450arom is expressed in the early postnatal testicular Leydig cells and spermatogonia. Even though the aromatase complex is required for estrogen synthesis, its biological relevance is also related to the regulation of the balance between androgens and estrogens in different tissues. Knockout mouse models of aromatase (ArKO) and estrogen receptors (ERKOα, ERKOβ, and ERKOαβ) provide an important tool to study the effects of estrogens on the male reproductive physiology including the gonadal axis. High basal serum FSH levels were reported in adult aromatase-deficient men, suggesting that estrogens are involved in the negative regulatory gonadotropin feedback. However, normal serum gonadotropin levels were observed in an aromatase-deficient boy, suggesting a maturational pattern role of estrogen in the regulation of gonadotropin secretion. Nevertheless, the role of estrogens in primate testis development and function is controversial and poorly understood. This review addresses the role of estrogens in gonadotropin secretion and testicular physiology in male humans especially during childhood and puberty.

Second surgery for recurrent unilateral endometriomas and impact on ovarian reserve: a case-control study

To investigate the impact on ovarian reserve of second laparoscopic surgery for recurrent unilateral endometriomas. Case-control study. University teaching hospital. This study included patients who underwent stripping of endometriomas (diameter ≥4cm) and were followed-up at our institution. Case subjects had second surgery for recurrent unilateral endometriomas (n = 18); control subjects had no recurrence and no second surgery (n = 18). This case-control study was based on a retrospective analysis of a prospectively collected database including patients who underwent surgery for endometriomas at our institution. The primary outcome of the study was to assess the changes in antimüllerian hormone (AMH) levels in each study group and between the two study groups. The secondary outcomes of the study were to assess the changes in basal FSH, antral follicle count (AFC), and ovarian volume in each study group and between the two study groups. In both study groups, primary surgery decreased AMH, increased basal FSH, and decreased the AFC of the operated ovary. Before second surgery, case subjects had AMH, basal FSH, and AFC similar to control subjects. After second surgery, case subjects had lower AMH, higher basal FSH, and lower AFC of the affected ovary than before surgery; the volume of the operated ovary was lower than that of the contralateral ovary. The laparoscopic stripping of recurrent ovarian endometriomas is associated with a high risk of ovarian reserve damage and ovarian failure. NCT02047838.

Association of luteinizing hormone chorionic gonadotropin receptor gene polymorphism (rs2293275) with polycystic ovarian syndrome.

Polycystic ovaries and irregular menstruation/anovulation are important diagnostic criteria along with hyperandrogenism as per the Androgen Excess Society-2006 criteria for polycystic ovarian syndrome (PCOS). In the etiopathogenesis of PCOS, one of the candidate genes causing ovarian failure is the luteinizing hormone (LH) chorionic gonadotropin hormone receptor (LHCGR). Our aim was to study the association of LHCGR polymorphism (rs2293275) with PCOS in our study population. Genetic case-control study from multiple gynecological centers from Hyderabad, a cosmopolitan city in South India. The study involved 204 women with PCOS and 204 healthy, sex-, and age-matched controls. Anthropometric and biochemical profiles were taken in a well-designed pro forma. Isolation of deoxyribonucleic acid (DNA) and genotype analysis were done for the entire study population using the polymerase chain reaction-restriction fragment length polymorphism method followed by 12% polyacrylamide gel electrophoresis. In this study, we have demonstrated an association between LHCGR (rs2293275) polymorphism and PCOS. The frequency of the G allele was 0.60 in PCOS and 0.49 in controls (odds ratio [OR] 1.531, confidence interval [CI] 1.16-2.01, and p-value=0.0026), which indicates that the G allele is associated with PCOS in our population. The GG genotype conferred a significant risk of developing PCOS (OR 3.36, CI 1.96-5.75, and p-value<0.0001). We found a significant association of the GG allele with body-mass index, waist to hip ratio, insulin resistance, LH, and LH/follicle-stimulating hormone (FSH) ratio in PCOS when compared with controls. The AA allele showed high basal FSH levels. This study suggests that LHCGR (rs2293275) polymorphism is associated with PCOS and could be used as a relevant molecular marker to identify women with the risk of developing PCOS in our population and may provide an understanding about the etiology of PCOS.

Couples dropping out of a reimbursed intrauterine insemination program: what is their prognostic profile and why do they drop out?

To evaluate whether baseline characteristics and prognostic profiles differed between couples who drop out from intrauterine insemination (IUI) and couples that continue IUI, and the reasons for couples dropping out from IUI programs. Retrospective observational cohort study. Fertility centers. Consecutive subfertile couples undergoing IUI. None. Characteristics and prognosis of ongoing pregnancy after IUI at the start of treatment of couples that dropped out compared with couples that continued treatment or achieved an ongoing pregnancy. We studied 803 couples who underwent 3,579 IUI cycles of whom 221 couples dropped out (28%). Couples dropping out completed 2.8 (SD ±1.4) cycles per couple compared with 4.5 (SD ±2.3) cycles per couple for those continuing treatment. Couples dropping out had a higher female age, longer subfertility duration, and higher basal FSH. Mean prognosis to achieve an ongoing pregnancy after IUI at start of treatment was 7.9% (SD ±2.4) per cycle for couples who dropped out and 8.5% (SD ±2.5) per cycle for couples continuing treatment. Of the dropouts, 100 couples (45%) were actively censored from the IUI program, 87 couples (39%) because of poor prognosis; 121 couples (55%) were passively censored from the program, of whom 62 (28%) dropped out owing to personal reasons; 59 couples (27%) were lost to follow-up. We found significant differences in prognostic profile between couples continuing treatment and couples dropping out, although these differences seem limited from a clinical perspective. We conclude that overestimation of ongoing pregnancy rates after IUI due to couples dropping out is limited.

FSH receptor polymorphism predicts outcome of ovulation induction in WHO-II anovulatory subfertility

The classical treatment algorithm in normogonadotropic (WHO-II) anovulatory infertility constitutes ovulation induction using clomiphene citrate as first-line and exogenous gonadotrophins (exFSH) as second-line therapy. Applying the 2003 Rotterdam criteria about 91% of WHO-II anovulatory patients are diagnosed with polycystic ovary syndrome (PCOS). A polymorphic variant of the FSH receptor (rs6166, Asn680Ser) has been associated with changes in the phenotype of women with PCOS i.e., higher basal FSH and LH levels and higher Testosterone levels. The present study aims to assess the influence of this polymorphic variant of the FSH receptor on the outcome of ovulation induction using CC and exFSH. The study was designed as a prospective longitudinal study (academic fertility unit) among 240 consecutive women with WHO-II anovulatory infertility. Results were replicated in an independent retrospective cohort of 185 PCOS patients (Rotterdam criteria). Patients were treated with Clomiphene, followed by second-line treatment with exFSH if necessary. Genotyping was performed in 159 of 240 (first cohort) and 185 (second cohort) women. Main outcome parameters were ovulation rate and ongoing pregnancy rate. Genotyped patients were similar to ungenotyped patients regarding clinical characteristics and outcome of ovulation induction. FSH receptor polymorphism (rs6166) was associated with clomiphene resistant anovulation. A pooled analysis of both cohorts showed 89% higher chance of anovulation (OR 1.9 [95%CI 1.1-3.3]) in homozygous carriers of the FSH receptor variant (Ser680). The pooled analysis did not show an association of ongoing pregnancy rates with FSH receptor genotype. FSH receptor polymorphism is associated with anovulation during treatment with clomiphene citrate. Therefore, FSH receptor genotyping may find its way into clinical practice in order to devise treatment algorithms that are better tailored to the individual patient.

To assist or not to assist embryo hatching

At early stages of development, the human embryo is protected by a surrounding two-layer coating—the zona pellucida. As the embryo develops further, this coating becomes thinner and, at the blastocyst stage, the thin coating is broken off and the embryo ‘hatches’ such that it can implant into the uterine wall. Following in vitro fertilization and in vitro growth, many embryos do not implant after embryo transfer. Cultured embryos are known to hatch and implant at a lower rate than naturally developed embryos in vivo. This lower hatching rate could be attributed to a thicker zona pellucida. A thicker zona has, for instance, been seen in older women and women with high basal FSH levels. It was therefore suggested that making a hole in or thinning of this outer layer may help embryos to ‘hatch’, thus increasing the implantation rates. In 1990 such an assisted hatching procedure was developed (Cohen, 1991).

IVF treatment should not be postponed for patients with high basal FSH concentrations

This study determined the influence of inter-cycle variation of basal FSH concentrations on IVF treatment results, in patients with a history of high basal FSH. Patients underwent at least two IVF cycles, one with basal serum FSH ⩾10IU/l and the other at least 3IU/l lower (interval between cycles being <1year when the second cycle had the elevated FSH). A subanalysis was performed in patients with exceptionally large differences in values (⩾16IU/l and ⩽12IU/l). IVF outcomes were compared according to basal FSH concentrations in two consecutive cycles. Seventy-six patients met the inclusion criteria. Mean basal serum FSH were 15.0±3.6IU/l in the 'high FSH' group (range 12-24IU/l) and 9.0±3.0IU/l in the 'low FSH' group (range 5-14IU/l). Patient age, oestradiol at HCG administration, number of collected oocytes, fertilization and clinical pregnancy rates were similar for all cycles compared. Analysis of the subgroup with exceptionally large differences of basal FSH concentration yielded similar results. Neither high nor low basal serum FSH values were associated with IVF outcome in patients with reduced ovarian reserve and previously determined high basal FSH concentrations. Ovarian stimulation need not be delayed until FSH declines.

Does early follicular serum prolactin levels effect IVF cycle outcomes?

OBJECTIVE: The aim of this study was to evaluate the effect of high early follicular phase serum prolactin levels on ovarian stimulation dynamics and outcomes in patients undergoing in vitro fertilization treatment. DESIGN: Retrospective analysis. MATERIALS AND METHODS: A total of 1009 patients who undergone IVF treatment, during 2006-2008 were analyzed. Basal prolactin, FSH, LH and E2 levels were measured in IVF cycles just before ovarian stimulation. Controlled ovarian stimulation was performed using the daily GnRH antagonist and recombinant FSH preparates. Patient with high basal FSH levels (≥18 mIU/ml) and older than 42 years of ages were excluded. Patients were cathegorized into two groups; study group (n=205); with PRL levels ≥ 25 ng/mL, and the control group (n=804); with normal PRL levels (<25 ng/mL). IVF cycle outcome parameters were evaluated. RESULTS: 1009 couples with different infertility etiologies included in this study. 911 embryo transfer cycle was performed. There were no significant differences seen in the age, infertility duration, basal LH levels, basal E2 levels, TSH, FT4, FT3, thyroid antibody levels between two groups. Basal FSH levels were significantly lower in the study group. Although there were no statistically differences, total dosage of recFSH was lower in study group than control group. Also daily dosage of rec FSH was significantly lower. The pregnancy rates were similar (39.2% vs 41.7%) in both groups. Results are given in Table.1. It has been shown that there is a negative correlation between PRL and basal FSH (p<0.01). Also the negative correlation was shown between PRL and total dosage of gonadotropins used (p<0.05) and daily dosage of gonadotrophins(p<0.01). CONCLUSIONS: These data confirm that there is a negative correlation between PRL and FSH levels. PRL may play beneficial effect on ovarian stimulation in IVF cycles.Table 1MeansStudy Group(n=205)Control Group(n=804)p valuesAge32.6±4.633.2±4.70.10B.FSH7.0±2.77.7±3.00.001∗B.LH5.4±2.45.3±2.60.61B.E250.4±26.447.5±16.90.13B.PRL34.7±12.914.5±4.8<0.001∗TSH1.9±1.61.7±1.00.08Total recFSH dose2267±6822370±7330.06Daily recFSH dose316±64327±680.03∗Days of Stimulation7.2±1.37.3±1.40.40Peak E21382±9021353±9330.68No.of retrieved oocytes9.7±7.48.8±7.10.12No.of MII oocytes7.8±6.07.3±5.90.27No.of transferred embryos2.6±0.72.5±0.70.25Pregnancy Rate39.2%41.7%0.16 Open table in a new tab

Relationship between women's age and basal follicle-stimulating hormone levels with aneuploidy risk in in vitro fertilization treatment

To assess the relationship of age and basal FSH level to the genetic quality of the embryo and the association with IVF treatment outcome. Prospective observation study. A major inner London fertility clinic in the United Kingdom. One hundred fifty-one women who underwent IVF treatment cycles in conjunction with preimplantation genetic diagnosis for aneuploidy screening before fresh embryo transfer, between July 2003 and July 2005. Basal FSH levels (days 2-4) were determined at an earlier cycle, and women were divided into two groups: high basal FSH (>or=10 IU/L) and low basal FSH (<10 IU/L). Chromosome analysis was performed on a single blastomere by using fluorescence in situ hybridization. Percentage of aneuploid embryos. The percentage of aneuploid embryos was not statistically significantly different between the high- (50.0%, n = 32) and low- (50.2%, n = 119) basal FSH groups. However, the percentage of aneuploid embryos was statistically significantly higher (56.2%, n = 109) for women aged >or=38 years, as compared with women <38 years of age (37.5%, n = 42), independent of basal FSH levels. Elevated basal FSH levels reflect lower ovarian reserve but have no association with genetic quality of embryos. The percentage of aneuploid embryos is increased with advanced maternal age.

Modern embryo transfer catheters and pregnancy outcome: a prospective randomized trial

Embryo transfer (ET) is the final crucial step in IVF treatment. The type of catheter used can affect the pregnancy rate (PR). In this prospective, randomized trial we compared the clinical PR between the Wallace and the Cook K-Jet embryo transfer catheters. Prospective, randomized clinical trial. A National Health Service Assisted Reproduction Unit. One hundred fifty women undergoing a fresh ET. Age more than 40 years, a high basal FSH, a previous difficult ET, or more than six previous ETs were the exclusion criteria. Women undergoing a fresh ET were randomized at the time of ET to either the Cook K-Jet or Wallace embryo transfer catheter. The randomization was stratified according to age and the number of previous ETs. Clinical PR. There was no significant difference in the clinical PR between the Wallace and the Cook catheters (22/75 [29.3%] and 23/75 [30.6%], relative risk [RR]: 0.96 [95% confidence interval 0.58-1.58]). There is no significant difference in the PRs achieved by modern, soft, double-lumen ET catheters.

Repeated testing of basal FSH levels has no predictive value for IVF outcome in women with elevated basal FSH

It is a common practice to repeatedly test the level of basal FSH early in the cycle and to start IVF treatment only when the FSH level is below a certain threshold value. This is based on the idea that these women will respond better to ovarian stimulation when the basal FSH level is lower at the start of the cycle. The aim of this study is to assess the value of this practice. Between January 1995 and January 2003, 39 women were identified. These women underwent two IVF treatment cycles within a 12 month period. The basal FSH level prior to each of these cycles was known to have changed. The treatment cycles were divided into cycles with a high basal FSH (> or =10 IU/l) and cycles with a low basal FSH (<10 IU/l). The 39 women underwent a total of 78 treatment cycles (in the first cycle 20 had elevated level of FSH and 19 had low FSH and vice versa in the second cycle). Therefore, there were 39 cycles with high FSH and 39 cycles with low FSH. There was obviously no live birth in the first treatment cycle, hence the reason for the patient undergoing another treatment cycle within 12 months of the first one. In the high FSH group, six became pregnant [pregnancy rate (PR) = 15.4%] and five delivered [live birth rate (LBR) = 12.8%]. In the low FSH group, three became pregnant (PR = 7.7%) and two delivered (LBR = 5.1%). The difference in PR and LBR, however, was not significant. Neither were there significant differences between the two groups with regard to the number of oocytes collected, oocytes fertilized, embryos transferred or miscarriage rate. The results of this study reveal that women who are poor responders or with reduced ovarian reserve have a poor outcome and repeatedly testing them will add no value. Cycling women with a history of elevated FSH should be offered treatment without further delay. Delaying treatment for these women could be counterproductive, as they may have to wait for many months, during which time they are getting older and closer to their menopause.

Bioactive FSH May Have Value as a Marker for Ovarian Reserve in Patients With Elevated Serum FSH and Normal Basal Antral Follicle Counts

ObjectiveTo evaluate the bioactivity of FSH in women with paradoxically high serum immunoactive basal FSH levels and otherwise “normal” ovarian reserve as determined by ultrasound screening and response to gonadotropin stimulation.DesignCase Series at a large academic reproductive center.Materials and methodsWe compared immunoactive basal FSH levels (immulite assay (DPC)) and bioactive FSH levels in CHO cells transfected with the FSH receptor in two groups of women. Group 1 consisted of two patients with an elevated basal serum immunoactive FSH (> 13 mIU/mL), a normal basal antral follicle count (bAFC >8), and a robust response to gonadotropin stimulation (> 10 follicles) during IVF-ET therapy. Group 2 consisted of five patients with elevated basal serum FSH levels and either abnormal bAFC (< 6 total in both ovaries) or poor response to gonadotropin stimulation (< 5 mature follicles).ResultsTabled 1Tabled 1ConclusionsFSH with disproportionately lower bioactivity compared with immunoactivity on assay testing may account for some paradoxically abnormal basal FSH assessments in women with otherwise normal ovarian reserve and response to fertility therapy. Patients with normal antral follicle counts and elevated serum FSH by immunoassays can be candidates for a trial of IVF-ET, and based on our small series, can anticipate a reasonable reproductive outcome. Larger trials are required to assess if a basal bioactive FSH assessment can prospectively predict which of these patients are good IVF-ET candidates, and what cutoff (if any) of FSH bioactivity is most appropriate to use clinically. Presented with an abnormal FSH, but a normal bAFC, bioactivity testing may reassure that ovarian reserve is intact. ObjectiveTo evaluate the bioactivity of FSH in women with paradoxically high serum immunoactive basal FSH levels and otherwise “normal” ovarian reserve as determined by ultrasound screening and response to gonadotropin stimulation. To evaluate the bioactivity of FSH in women with paradoxically high serum immunoactive basal FSH levels and otherwise “normal” ovarian reserve as determined by ultrasound screening and response to gonadotropin stimulation. DesignCase Series at a large academic reproductive center. Case Series at a large academic reproductive center. Materials and methodsWe compared immunoactive basal FSH levels (immulite assay (DPC)) and bioactive FSH levels in CHO cells transfected with the FSH receptor in two groups of women. Group 1 consisted of two patients with an elevated basal serum immunoactive FSH (> 13 mIU/mL), a normal basal antral follicle count (bAFC >8), and a robust response to gonadotropin stimulation (> 10 follicles) during IVF-ET therapy. Group 2 consisted of five patients with elevated basal serum FSH levels and either abnormal bAFC (< 6 total in both ovaries) or poor response to gonadotropin stimulation (< 5 mature follicles). We compared immunoactive basal FSH levels (immulite assay (DPC)) and bioactive FSH levels in CHO cells transfected with the FSH receptor in two groups of women. Group 1 consisted of two patients with an elevated basal serum immunoactive FSH (> 13 mIU/mL), a normal basal antral follicle count (bAFC >8), and a robust response to gonadotropin stimulation (> 10 follicles) during IVF-ET therapy. Group 2 consisted of five patients with elevated basal serum FSH levels and either abnormal bAFC (< 6 total in both ovaries) or poor response to gonadotropin stimulation (< 5 mature follicles). ResultsTabled 1Tabled 1 ConclusionsFSH with disproportionately lower bioactivity compared with immunoactivity on assay testing may account for some paradoxically abnormal basal FSH assessments in women with otherwise normal ovarian reserve and response to fertility therapy. Patients with normal antral follicle counts and elevated serum FSH by immunoassays can be candidates for a trial of IVF-ET, and based on our small series, can anticipate a reasonable reproductive outcome. Larger trials are required to assess if a basal bioactive FSH assessment can prospectively predict which of these patients are good IVF-ET candidates, and what cutoff (if any) of FSH bioactivity is most appropriate to use clinically. Presented with an abnormal FSH, but a normal bAFC, bioactivity testing may reassure that ovarian reserve is intact. FSH with disproportionately lower bioactivity compared with immunoactivity on assay testing may account for some paradoxically abnormal basal FSH assessments in women with otherwise normal ovarian reserve and response to fertility therapy. Patients with normal antral follicle counts and elevated serum FSH by immunoassays can be candidates for a trial of IVF-ET, and based on our small series, can anticipate a reasonable reproductive outcome. Larger trials are required to assess if a basal bioactive FSH assessment can prospectively predict which of these patients are good IVF-ET candidates, and what cutoff (if any) of FSH bioactivity is most appropriate to use clinically. Presented with an abnormal FSH, but a normal bAFC, bioactivity testing may reassure that ovarian reserve is intact.

Using the Antagonist Cetrotide 3 mg in the Luteal Phase Prior to IVF Stimulation Results in a Improved IVF Cycle Outcomes in Poor Responders and Decreased Ovarian Reserve Patients

Background: For many patients with high basal FSH or estradiol levels and/or patients with poor responses to gonadotropin stimulation for IVF, identifying an appropriate protocol to achieve an adequate response can be a challenge. Many low responders will stimulate very quickly to high doses of gonadotropins and make few mature follicles or have significant asynchrony in follicle sizes, especially in microdose Lupron protocols. Endogenous late luteal phase FSH levels may drive this asynchrony as well.

Ovulation induction with letrozole in gonadotrophin stimulation resistant women undergoing in vitro fertilization

To assess the clinical outcomes of aromatase inhibitors for stimulating poor responder women undergoing in vitro fertilization (IVF) protocol in whom high doses gonadotrophins treatment was unsuccessful. Retrospective analysis. 37 IVF patients with high basal concentrations of FSH(>13 mIU/mL) who had shown no response to vigorous gonadotrophin stimulation are reported. Patients were offered letrozole, 5 mg/day for 5 consecutive days starting on day 3 of the menstrual cycle. Ultrasonography was performed before initiation of treatment, on day 9 of menstrual cycle, and as required thereafter until the dominant follicle reached 18 mm in diameter. Ovulation was triggered with 10,000 IU of hCG, and oocyte pick-up was performed 34–36 hours later. Sixteen cycles (42%) were canceled because of no ovarian response. Five patients (24%) did not have IVF because of no oocyte retrieval. And four patients did not have ET because of failed fertilization. Twelve patients become an embryo transfer. Only one patient was pregnant. The clinical pregnancy rate was 1 of 12 (9%) per embryo transfer. Poor responders undergoing controlled ovarian hyperstimulation with letrozole in cycles with high basal FSH and who are vigorous gonadotrophin stimulation resistant will often show adequate ovarian response and reach oocyte retrieval and ET. The pregnancy rates, however, remain low. This intervention comparing to the cost of gonadotrophin protocols may have future implications for the treatment of poor responders.