The utility of serum inhibin B, anti-Müllerian hormone and insulin growth factor-1 in predicting a positive response to GnRH analogs for diagnosing central precocious puberty in girls

Objectives The use of inhibin B (INHB), anti-Müllerian hormone (AMH) and insulin-like growth factor-1 (IGF-1) in differentiating central precocious puberty (CPP) from non-CPP was evaluated. Methods In total, 115 Chinese girls were recruited (CPP: 44, non-CPP: 71). The diagnostic performance of INHB, AMH and IGF-1 in differentiating CPP from non-CPP was analyzed using receiver operating characteristic (ROC) curves. Results INHB levels were higher in the CPP group than in the non-CPP group (55.56 ± 22.42 vs. 32.97 ± 15.59 pg/mL; p<0.001). AMH levels were similar in the CPP and non-CPP groups (6.63 ± 3.74 vs. 5.70 ± 3.15 pg/mL; p=0.158), and IGF-1 levels were much higher in the CPP group than in the non-CPP group (290.75 ± 79.78 vs. 200.10 ± 54.01 pg/mL; p<0.001). The area under the ROC curve (AUC) was greatest for INHB (0.819, standard error (SE) 0.041), followed by IGF-1 (0.809, SE 0.047) and AMH (0.567, SE 0.057). Among the ROC curves including combinations of these parameters, the AUC for INHB + IGF-1 was 0.849 and that for INHB + AMH was 0.768. Conclusions Serum INHB and IGF-1 measurements could predict positive responses to gonadotropin-releasing hormone (GnRH) analog stimulation in girls with precocious puberty.

O-113 Effectiveness and treatment cost of assisted reproduction technology for women stimulated by gonadotropin in France: A cohort study using the National Health Database

Study question How effective is Assisted Reproduction Technology (ART) in terms of cumulative live birth rate (CLBR) in France, depending on the gonadotropin used? Summary answer Among 214,539 stimulations, originator follitropin-alfa was associated with significantly higher CLBR when compared to Highly Purified-Human Menopausal Gonadotropin (HP-HMG) and biosimilars. What is known already Deciding which type of gonadotropin to prescribe for a woman undergoing controlled ovarian stimulation (COS) remains difficult. The effectiveness of different gonadotropins is one factor to consider. However, studies comparing r-hFSH-alfa, its biosimilars and HP-HMG are scarce and are mostly based on a single ART treatment cycle and fresh embryo transfers. Some clinical trials have shown similar pregnancy, pregnancy loss, and live birth rates after fresh embryo transfer (ET) between HP-HMG and r-hFSH. However, because more oocytes are retrieved with r-hFSH when compared to HP-HMG, it is logical to hypothesize that the CLBR is higher with r-hFSH. Study design, size, duration A non-interventional study based on the French National Health System (SNDS) database was designed to assess the CLBR and treatment costs from the national payer perspective of four gonadotropin groups (originator follitropin-alfa (r-hFSH-alfa), its biosimilars, HP-HMG and r-hFSH-beta) used for COS cycles leading to oocyte pick-up (OPU) between 01/01/2013 and 31/12/2017 with a follow-up period up to 31/12/2018. The study compared CLBR, with originator r-hFSH-alfa as the reference. Participants/materials, setting, methods Women with COS cycles resulting in OPU with one of the specified gonadotropins were included. Data were extracted from billing and reimbursement records of outpatient healthcare consumption and national hospital discharge databases using a unique, anonymized patient number. CLBR was estimated using an Andersen–Gill model, adjusted for clinical baseline, stimulation and ET variables. Costs were reported as secondary outcomes. Main results and the role of chance 135,752 women (mean age 34.1), underwent 214,539 stimulations leading to OPU and contributed one (61.5%), two (24.8%), three (9.4%) or four (3.2%) COS cycles. COS cycles were stimulated with either Originator r-hFSH-alfa (46%), HP-HMG (29%), r-hFSH-beta (21%) or r-hFSH-alfa biosimilars (4%). Over the study period, CLBR reached 20.5%; 21.9% with originator r-hFSH-alfa, 17.9% with HP-HMG, 21.3% with r-hFSH-beta and 18.4% with r-hFSH-alfa biosimilars. After adjusting for age, pre-treatment, GnRH analog, ovulation triggering, luteal phase support, previous COS, fresh or frozen ET and type of center, as possible cofounding variables, the adjusted hazard ratio (HR) for CLBR (delivery [originator r-hFSH-alfa as reference]) was 0.88 (95% CI 0.86 to 0.95, p &lt; 0.0001) with HP-HMG; 0.98 (95% CI 0.95 to 1.00, p = 0.1020) with r-hFSH-beta, and 0.84 (95% CI 0.79 to 0.90, p &lt; 0.0001) with r-hFSH-alfa biosimilars. Although the mean acquisition cost of r-hFSH-alfa during the study was 33% higher than HP-HMG and 20% higher than r-hFSH-alfa biosimilars, the global ART management costs were only 4% higher than HP-HMG, 3% higher than r-hFSH-beta, and similar to r-hFSH-alfa biosimilars. Limitations, reasons for caution Patients were included only from oocyte pick-up, due to missing data in the SNDS database, meaning that it was not possible to estimate the proportion of cancelled cycles. Furthermore, as r-hFSH-alfa biosimilars were only available since 2015, results for biosimilars should be interpreted with caution. Wider implications of the findings This population-wide French study confirms other Real-World and meta-analysis evidence that CLBR is higher with originator r-hFSH-alfa than with HP-HMG or r-hFSH-alfa biosimilars, respectively, and are relevant for healthcare professionals to support gonadotropin treatment decision making. To further support this, the cost analysis should be completed by a cost-effectiveness analysis. Trial registration number Not applicable

Case Report: Ovulation Induction in Greater One-Horned Rhinoceros (Rhinoceros unicornis)

Despite a profound knowledge on reproduction biology in greater one-horned (GOH) rhinoceros, many individuals cope with sub or infertility or an-ovulatory estrous. At the same time, early and regular captive breeding is of high importance in female GOH rhinoceros due to their high prevalence to develop genital tract tumors with consequent cessation of reproduction. Thus, mature, an-ovulatory GOH rhinoceros represent a challenge for captive breeding programs and warrant for means of reliable ovulation induction. Here, we used hCG and GnRH analog histrelin to induce ovulation in an-ovulatory GOH rhinoceros. Upon ultrasound diagnosis of a preovulatory follicle hCG or GnRH were injected to induce ovulation (n = 11). As a result, 75% of the hCG (n = 6/8) and 33% of GnRH (n = 1/3) inductions resulted in ovulation. Ovulation occurred when fecal estrogen concentration increased before and pregnane concentration after induction. Thirty-six percent of all treatments (n = 4/11) failed to induce ovulation. When ovulation induction by hCG/GnRH injection failed, estrogen and pregnane concentrations were significantly lower compared to ovulatory estrous (P &lt; 0.001). Our results suggest that hCG and GnRH analog facilitate an easily applicable treatment to induce ovulation in females with behavioral but at times an-ovulatory estrous. Frequent use of hCG as an ovulation inducer might help to achieve pregnancies in genetically important but an-ovulatory GOH rhinoceroses.

Determinants of Final Height in Patients Born Small for Gestational Age Treated with Recombinant Growth Hormone

<b><i>Introduction:</i></b> About 8% of children born small for gestational age (SGA) do not reach a final height within the normal range. Recombinant human growth hormone (rhGH) has been shown to be effective in increasing the final height in children born SGA. Our objective was to identify predictive factors of final height in children born SGA treated with rhGH. <b><i>Materials and Methods:</i></b> In this retrospective study, conducted in a tertiary pediatric endocrinology referral center, we recruited all patients born SGA (defined as birth length or weight &#x3c;10th percentile) treated with rhGH for more than 12 months for whom final height data were available. Some patients had received gonadotropin-releasing hormone (GnRH) analog therapy. <b><i>Results:</i></b> We included 252 patients with an average birth length of −2.0 ± 0.7 SD and birth weight of −1.7 ± 1.0 SD. After 4.6 ± 2.8 years of rhGH treatment, their height increased from −2.2 ± 0.9 SD to −1.5 ± 0.9 SD. In multivariate analysis, we identified 8 factors that predict 46% of the final height, namely, cause of SGA (<i>p</i> &#x3c; 0.0001), GnRH analog therapy &#x3e;2 years (<i>p</i> = 0.006), birth length (<i>p</i> &#x3c; 0.02), height at the start of rhGH (<i>p</i> &#x3c; 0.0001), IGF-1 level at the start of rhGH (<i>p</i> = 0.0002), growth velocity during the 1st year of treatment (<i>p</i> = 0.0002), and age and height at the onset of puberty (<i>p</i> &#x3c; 0.0001, <i>p</i> = 0.0007, respectively). <b><i>Conclusion:</i></b> In this large cohort of SGA patients who had reached their final height, we were able to confirm that growth hormone increases final height in short SGA children. In addition, we identified several factors associated with a better response to growth hormone treatment.

Central Precocious Puberty in Boys and Girls: Similarities and Differences

Central precocious puberty (CPP) is due to the premature activation of the hypothalamic–pituitary–gonadal axis, which is responsible for the appearance of secondary sexual characteristics. It occurs before the age of 8 and 9 in girls and boys, respectively. CPP shows higher incidence in females than in males. Causes of CPP are similar in both sexes, but the idiopathic form is more frequent in girls, while organic forms are more frequent in males. Recent studies demonstrated a role of some genetic variants in the pathogenesis of CPP. The diagnostic evaluation based on accurate physical examination, assessment of the pituitary–gonadal axis, pelvic sonography in girls, and determination of bone age. Magnetic resonance of the central nervous system should be done in all boys and selected girls. Since the 1980s, pharmacologic treatment involves the use of gonadotropin-releasing hormone (GnRH) analogs. These drugs are characterized by few side effects and long-term safety. Many data are available on the outcome of GnRH analog treated female patients, while poor data are reported in boys. Adult height is improved in both sexes.

Is Anti-Müllerian Hormone a Marker of Ovarian Reserve in Young Breast Cancer Patients Receiving a GnRH Analog during Chemotherapy?

Introduction: Anti-Müllerian hormone (AMH) is the most reliable biomarker of ovarian reserve; however, its role in predicting ovarian recovery after chemotherapy is unclear. Administration of a GnRH analog (GnRHa) during chemotherapy significantly reduces the ovarian failure rate and increases the pregnancy rate. The available data on the behavior of AMH during concurrent administration of chemotherapy and GnRHa are inconsistent. We investigated whether concurrent administration of triptorelin and adjuvant chemotherapy might reduce the expected drop of AMH. Methods: Eligible patients were premenopausal women aged <40 years, with a diagnosis of early breast cancer, and candidates to 4–8 cycles of adjuvant chemotherapy. Triptorelin (3.75 mg i.m.) was started before chemotherapy and administered every 4 weeks thereafter. The principal endpoint was the proportion of patients with an AMH percent change ≤50% between 12 months after chemotherapy and basal levels. The secondary endpoint was the proportion of patients achieving postchemotherapy AMH levels above the threshold of 0.2 ng/mL. Results: Fifty patients were enrolled, 31 of whom had blood samples available at baseline and 1 year after the end of chemotherapy. AMH decreased to nearly undetectable levels after chemotherapy and recovered after 12 months, but they did not exceed 1 tenth of the pretreatment levels. As for the secondary endpoint, 15 of the 31 patients recovered AMH levels above the threshold. Conclusions: This study did not reach its principal endpoint; however, the rate of 48% of patients who recovered AMH above threshold levels favorably compared with those in studies without concurrent GnRHa, supporting a better recovery of AMH with triptorelin.