Recombinant or urinary follicle-stimulating hormone? A cost-effectiveness analysis derived by particularizing the number needed to treat from a published meta-analysis

Objective: To demonstrate that particularizing pooled results of a meta-analysis can derive incremental cost effectiveness of superovulation with recombinant follicle-stimulating hormones (rFSH) vs. the highly purified urinary form (uFSH) for assisted conception.

Design: A retrospective study.

Setting: An assisted conception unit in the United Kingdom.

Patient(s): One hundred forty-five fresh in vitro fertilization (IVF) and 58 fresh intracytoplasmic sperm injection (ICSI) cycles.

Intervention(s): rFSH vs. uFSH.

Main Outcome Measure(s): Incremental cost-effectiveness (i.e., cost needed to treat, or CNT) and budget-impact analyses of rFSH vs. uFSH.

Result(s): In women less than 30 years old, the clinical pregnancy rate was 37.7% (95% CI 24.8%–52.1%), the particularized number needed to treat (pNNT) was −19, and the cost needed to treat was £5070.51 (£3660.53 to £7619.32). For the 30- to 35-year-old age group, the clinical pregnancy rate was 29.9% (95% CI 20.0%–41.4%), the particularized number needed to treat was −24, and CNT was £7335.59 (£5284.11 to £10,941.22). For the 36- to 40-year-old age group, the clinical pregnancy rate was 30.6.0% (95% CI 19.6%–43.7%), the particularized number needed to treat was −23.0, and the CNT was £8569.67 (£5998.70 to £13,413.24).

Conclusion(s): The CNT and thus the budget impact analyses (the extra number of cycles that can be funded by the CNT) both increase directly with age of the patient, and inversely with the clinical pregnancy rate.     

Serum antimüllerian hormone/müllerian-inhibiting substance appears to be a more discriminatory marker of assisted reproductive technology outcome than follicle-stimulating hormone, inhibin B, or estradiol

OBJECTIVE: To test the hypothesis that the concentration of early follicular phase serum antimullerian hormone (AMH) or mullerian-inhibiting substance (MIS) is a useful marker of ovarian response and assisted reproductive technology (ART) outcome. DESIGN: Retrospective analysis of day 3 serum samples drawn before treatment. SETTING: Private ART program. PATIENT(S): One hundred nine consecutive serum samples from women younger than 42 years of age who were undergoing ovulation induction for IVF. INTERVENTION(S): Follicular aspiration for IVF after ovarian stimulation with FSH in a down-regulated cycle using GnRH-a treatment. MAIN OUTCOME MEASURE(S): Correlations between day 3 serum AMH/MIS, E2, FSH, inhibin B levels, and IVF outcome (i.e., number of retrieved mature oocytes, number and quality of embryos obtained, ongoing clinical pregnancy rates). Multivariate regression analysis on categorical data was performed to describe a predictive model of clinical pregnancy outcome. RESULT(S): Mean serum AMH/MIS value for clinical pregnancy (n = 38) was 2.4 ng/mL, in comparison to 1.1 ng/mL for those who did not become pregnant (n = 71). No differences were noted in mean values for day 3 FSH, inhibin B, or E2 between groups. Multivariate regression analysis demonstrated that day 3 serum AMH/MIS had the greatest independent contribution in predicting pregnancy outcomes. CONCLUSION(S): These data demonstrate a strong association between day 3 serum AMH/MIS level and IVF outcome in women younger than 42 years of age. Higher AMH/MIS concentrations are associated with a greater number of mature oocytes, a greater number of embryos, and ultimately a higher clinical pregnancy rate. Furthermore, AMH/MIS may offer greater prognostic value than other currently available serum markers of ART outcome.     

Combination of polymorphisms in luteinizing hormone β, estrogen receptor β and progesterone receptor and susceptibility to infertility and endometriosis

Objectives

To determine whether the combination of PR (PROGINS), ERβ G + 1730A and/or LHβ G1502A polymorphisms in infertile women with and without endometriosis and in a control group increases the risk of infertility and/or endometriosis.

Study design

Case-control study including 201 infertile women with endometriosis, 80 infertile women without endometriosis and 206 fertile women as control group. PROGINS was identified by PCR (polymerase chain reaction) and ERβ G + 1730A and LHβ G1502A were identified by PCR-RFLP (restriction fragment length polymorphism).

Results

A statistically significant difference was found for the combination of LHβ + ERβ polymorphisms among infertile patients with endometriosis and control group (p = 0.003, OR = 2.468), among infertile patients with endometriosis I/II and control group (p = 0.002, OR = 3.081), among infertile patients with endometriosis III/IV and control group (p = 0.035, OR = 2.136) and for the combination of LHβ + PROGINS polymorphisms among infertile patients with endometriosis I/II and control group (p = 0.014, OR = 3.081). However, the odds of developing endometriosis are not enhanced in the presence of the two polymorphisms, being similar to the odds when only LH polymorphism is present.

Conclusions

Individually, the presence of LHβ G1502A and ERβ G + 1730A polymorphisms is associated with infertility and endometriosis associated infertility. However, when two polymorphisms are present in the same individual it does not appear to increase the chance of developing endometriosis or infertility.     

Serum inhibin B and anti-Müllerian hormone are not superior to follicle-stimulating hormone as predictors of the presence of sperm in testicular fine-needle aspiration in men with azoospermia

OBJECTIVE: To compare FSH, inhibin B (INHB), and anti-Müllerian hormone (AMH) as predictors of the recovery of sperm in testicular fine-needle aspiration biopsy (FNA) performed in men with azoospermia. DESIGN: Cross-sectional, clinical study. SETTING: Academic Unit of Reproductive Endocrinology. PATIENT(S): Fifty-one men with azoospermia and 31 controls. INTERVENTION(S): Testicular FNA. MAIN OUTCOME MEASURE(S): Serum FSH, INHB, and AMH levels. RESULT(S): Clinical diagnoses in men with azoospermia were idiopathic nonobstructive azoospermia (n = 34, 67%), cryptorchidism (n = 4, 8%), varicocele (n = 3, 6%), and other diagnoses (n = 10, 16%). In pairwise comparison of receiver operating characteristic curves, none of FSH (area under curve 0.716), INHB (0.610), AMH (0.565), or volume of the larger testis (0.693) was proved to be superior to the others as predictor of sperm retrieval during an FNA procedure. Similarly, in a logistic regression analysis, none of FSH, AMH, INHB, or volume of the larger testis could predict presence of sperm in FNA. CONCLUSION(S): Serum INHB and AMH, as well as their combination, are not superior to FSH as predictors of the presence of sperm in testicular FNA in men with azoospermia and should not be used for this purpose.     

Progesterone in pregnancy; receptor–ligand interaction and signaling pathways

Progesterone is indispensable in creating a suitable endometrial environment for implantation, and also for the maintenance of pregnancy. Successful pregnancy depends on an appropriate maternal immune response to the fetus. Along with its endocrine effects, progesterone also acts as an “immunosteroid”, by contributing to the establishment of a pregnancy protective immune milieu. Progesterone plays a role in uterine homing of NK cells and upregulates HLA-G gene expression, the ligand for NK inhibitory and activating receptors. At high concentrations, progesterone is a potent inducer of Th2-type cytokines as well as of LIF and M-CSF production by T cells. A protein called progesterone-induced blocking factor (PIBF), by inducing a Th2-dominant cytokine production mediates the immunological effects of progesterone. PIBF binds to a novel type of the IL-4 receptor and signals via the Jak/STAT pathway, to induce a number of genes, that not only affect the immune response, but might also play a role in trophoblast invasiveness.     

Recombinant follicle-stimulating hormone (follitropin alfa) for ovulation induction in Japanese patients with anti-estrogen-ineffective oligo- or anovulatory infertility: results of a phase II dose–response study

Purpose  

To determine the optimal regimen of recombinant human follicle-stimulating hormone (r-hFSH) for ovulation induction (OI) in Japanese women with amenorrhea I or anovulatory infertility.     

Investigation of soluble anti-Müllerian hormone receptor type 2 as a biomarker for diagnosis of female fertility disorders

Research questionThe ectodomain of the anti-Müllerian hormone (AMH) type 2 receptor is shed by proteases under certain conditions, which makes it measurable in the blood. The aim of this study was to identify correlations of soluble anti-Müllerian hormone receptor type 2 (sAMHR2) with other sex hormone concentrations and to assess whether sAMHR2 may serve as a new biomarker in fertility disorders.DesignIn a retrospective cross-sectional study of women (n = 186) with different gynaecological–endocrinological disorders, mixed-effect models were used to analyse the correlation with established diagnostic hormone tests. Receiver operating characteristic curve analysis was performed to assess the diagnostic performance.ResultsThere was a strong correlation of sAMHR2 with LH (r = 0.898) and FSH (r = 0.846) and a moderate correlation of AMH with testosterone (r = 0.666) and androstenedione (r = 0.696) (all P < 0.001). In diagnoses of polycystic ovary syndrome (PCOS), AMH showed the best performance (area under the curve [AUC] 0.981, cut-off 4 ng/ml) with 96% sensitivity and 94% specificity. sAMHR2 concentrations and sAMHR2/AMH ratios were elevated in women with ovarian insufficiency, compared with all other study groups, including post-menopausal women on hormone replacement therapy. Highest sensitivity and specificity (100% and 98.2%, respectively) were achieved with sAMHR2/AMH ratio for the diagnosis of post-menopausal status (cut-off 68.85). The sAMHR2/AMH ratio (AUC 0.997) had a better performance than sAMHR2 (AUC 0.947), FSH (AUC 0.989) and LH (AUC 0.967).ConclusionsThe sAMHR2/AMH ratio may serve as a useful biomarker for infertility diagnostics to identify post-menopausal women.