Soluble urokinase plasminogen activator receptor (suPAR) as a biomarker of early pregnancy location and viability compared with hCG, progesterone and estradiol.

A circulating biomarker of early pregnancy outcome independent of ultrasonography and gestational age is a coveted goal. This study evaluated soluble urokinase plasminogen activator receptor (suPAR), a well-described marker of inflammation and immunological activation, for this purpose, and compared it with established early pregnancy biomarkers of the luteoplacental phase: progesterone, estradiol and hCG. We merged data from two prospective first trimester cohorts to conduct a case-control study comparing these analytes in women who had either a live birth, a miscarriage or an ectopic pregnancy. The ability to predict pregnancy location and viability was assessed by areas under the receiver operating characteristic curves (AUC). Comparing women irrespective of gestational age with a live birth, miscarriage or ectopic pregnancy showed significantly lower suPAR values in the latter group (2.4 vs. 2.4 vs. 2.0 µg/L, p = 0.032, respectively), as were all other analytes. Before 6 weeks' gestation, suPAR was significantly inferior to progesterone, estradiol and hCG in pregnancy location and viability prediction (in 124 pregnancies, suPAR AUClocation = 0.69 [CI: 0.54-0.83] and AUCviability = 0.58 [CI: 0.48-0.69], while progesterone AUClocation = 0.95 [CI: 0.87-1.00] and AUCviability = 0.84 [CI: 0.75-0.92]). After 6 weeks' gestation, suPAR prediction improved but was inferior to hCG, progesterone and estradiol (in 188 pregnanices, suPAR AUClocation = 0.71 [CI: 0.63-0.78] and AUCviability = 0.70 [CI: 0.63-0.78] compared with hCG AUClocation = 0.96 [CI: 0.93-0.99] and AUCviability = 0.96 [CI: 0.93-0.98]). Collectively, suPAR is less useful as a predictor of early pregnancy outcome than hCG, progesterone and estradol.

Contribution of recruitable follicles to circulating anti-Müllerian hormone levels following maximal gonadotrophin stimulation in patients with limited ovarian reserve.

In women, the majority of anti-Müllerian hormone (AMH) measured in serum originate from small antral follicles measuring 2-10 mm. In gonadotrophin-stimulated cycles prior to assisted reproductive technology (ART), most of the recruitable follicles develop beyond 10 mm in size and thus lose their AMH secretion capacity causing declining serum AMH levels. The aim of this study was to define the residual serum AMH level after elimination of the AMH producing recruitable follicles following maximal gonadotrophin stimulation. We measured serum AMH and number of follicles according to size at several time points during a cycle of maximal gonadotrophin stimulation (fixed dose of 300 IE HP-hMG) in 107 women with low AMH (median AMH 5 pmol/L, interquartile range (IQR) 3.3-8.3). We found that AMH decreased gradually and reached a minimum level of -55.4% (95% CI -59.6; -50.7) of the baseline value four days after ovulation trigger. Our findings suggest that the residual AMH production origins from pre-antral and small antral follicles not visible by sonography and that they account for up to 40% of the circulating AMH.

Serum anti-Müllerian hormone concentration before and after salpingectomy for ectopic pregnancy.

RESEARCH QUESTION: Does salpingectomy for ectopic pregnancy affect the ovarian reserve measured by changes in pre- and post-operative levels of anti-Müllerian hormone (AMH)? DESIGN: This is a prospective observational multicentre study of 64 women treated with salpingectomy for an ectopic pregnancy. AMH was measured in serum samples collected at admission before salpingectomy and at follow-up (median time to follow-up [interquartile range] was 3 [3-4] months). Changes in serum AMH levels were investigated using Wilcoxon signed-rank test and the relationship between changes in AMH and age, time to follow-up, and pre-operative serum AMH level was investigated using linear regression analysis. The biological variation of AMH was also calculated. RESULTS: Serum AMH levels did not differ significantly before and after salpingectomy (median ∆AMH [follow-up value minus admission value] 0.40 pmol/l, interquartile range -2.0 to 4.0 pmol/l). ΔAMH was independent of age, time to follow-up and pre-operative serum AMH level. The intra-individual biological variation for AMH ranged from 12.1% to 26.3%, depending on time between the two samples. CONCLUSIONS: This is the first paired study to investigate serum AMH values before and after salpingectomy in an unselected population of women presenting with an ectopic pregnancy, including both patients who conceived naturally and following fertility treatment. It was found that salpingectomy for ectopic pregnancy had no short-term effect on serum AMH levels, and changes in AMH levels were independent of age, time to follow-up, and pre-operative serum AMH level. Furthermore, the study demonstrated a 6-month biological variation of AMH of less than 30%.

The use of anti-Müllerian hormone for controlled ovarian stimulation in assisted reproductive technology, fertility assessment and -counseling.

Ovarian reserve can be determined by serum anti-Müllerian hormone (AMH) level and/or antral follicle count before controlled ovarian stimulation. The aim of controlled ovarian stimulation is to achieve an appropriate number of mature follicles and avoid complications such as ovarian hyperstimulation syndrome. Measurement of the ovarian reserve is useful for clinicians as it predicts the ovarian response to controlled ovarian stimulation. Further, it assists in giving the patient realistic expectations regarding the treatment. By determining the ovarian reserve, the most appropriate stimulation protocol and gonadotropin dose can be chosen specifically for each woman enabling so-called "individualized treatment" in line with the personalized treatment concept. Many benefits come with using AMH as a biomarker for ovarian reserve; the hormone is considered fairly cycle independent apart from a small decrease in the late follicular phase and there is no inter-observer variance. However, the use of AMH also has limitations; since the implementation of AMH in fertility treatment several AMH assays have been developed. This has made direct comparisons of AMH serum levels complicated. Currently, no international standardized assays exist. AMH is a valid predictor of the ovarian response to controlled ovarian stimulation and to some extent the chance of pregnancy in relation to assisted reproductive technology, but AMH is less optimal in prediction of spontaneous pregnancy and live birth after assisted reproductive technology. Accordingly, AMH can be used to optimize gonadotropin stimulation in fertility treatment, but is not recommended as a screening tool in the general population.

[The use of anti-Müllerian hormone in fertility treatment].

The need for fertility treatment in Denmark is increasing, one of the main causes being postponed parenthood. Ovarian reserve is determined by the anti-Müllerian hormone (AMH) level and by antral follicle count. Both tests can predict the ovarian response to gonadotropin treatment prior to in vitro fertilization (IVF) and are used to individualize ovarian stimulation to achieve an appropriate number of follicles and to avoid ovarian hyperstimulation. A new assay detects low values of AMH and may predict who will benefit from IVF, and who should be referred directly to oocyte donation.

Sexual and reproductive health in Greenland: evaluation of implementing sexual peer-to-peer education in Greenland (the SexInuk project).

BACKGROUND: For decades, the rates of sexually transmitted infections (STIs), such as gonorrhoea, chlamydia and syphilis, have increased in Greenland, especially within the young age groups (15-29 years). From 2006 to 2013, the number of abortions has been consistent with approximately 800-900 abortions per year in Greenland, which is nearly as high as the total number of births during the same period. Previous studies in Greenland have reported that knowledge about sexual health is important, both as prevention and as facilitator to stop the increasing rates of STIs. A peer-to-peer education programme about sexual health requires adaption to cultural values and acceptance among the population and government in order to be sustainable. OBJECTIVE: Formative evaluation of a voluntary project (SexInuk), in relation to peer-to-peer education with focus on sexual health. Two workshops were conducted in Nuuk, Greenland, to recruit Greenlandic students. DESIGN: Qualitative design with focus group interviews (FGIs) to collect qualitative feedback on feasibility and implementation of the project. Supplemented with a brief questionnaire regarding personal information (gender, age, education) and questions about the educational elements in the SexInuk project. Eight Greenlandic students, who had completed one or two workshops, were enrolled. RESULTS: The FGIs showed an overall consensus regarding the need for improving sexual health education in Greenland. The participants requested more voluntary educators, to secure sustainability. The articulation of taboo topics in the Greenlandic society appeared very important. The participants suggested more awareness by promoting the project. CONCLUSIONS: Cultural values and language directions were important elements in the FGIs. To our knowledge, voluntary work regarding peer-to-peer education and sexual health has not been structurally evaluated in Greenland before. To achieve sustainability, the project needs educators and financial support. Further research is needed to investigate how peer-to-peer education can improve sexual and reproductive health in Greenland.

Recent progress in the utility of anti-Müllerian hormone in female infertility.

PURPOSE OF REVIEW: To discuss the recent developments in the utility of anti-Müllerian hormone (AMH) in the context of female infertility. RECENT FINDINGS: AMH measurements have entered the clinical practice in counseling of women before in-vitro fertilization (IVF) treatment. AMH measurements can predict both poor and hyperresponse, and can enable clinicians to individualize the treatment strategies. In natural conception, AMH is a good predictor of age at menopause, but it is unclear whether AMH correlates with the fecund ability in the normal population. AMH has also proven its utility in the assessment of ovarian damage due to gonadotoxic treatment or ovarian surgery. Lastly, AMH might assist in the initial diagnosis of oligomenorrhea or amenorrhea, as high levels of AMH are suggestive of polycystic ovarian syndrome and seem to correlate with the severity of the syndrome. SUMMARY: AMH is a glycoprotein secreted by the granulosa cells of small growing follicles and indirectly reflects the primordial follicle pool. The ovaries contain a limited number of primordial follicles and their depletion marks the menopause. Thus, the remaining primordial follicle pool is referred to as the ovarian reserve. The clearest data for the clinical utility of AMH is in the context of IVF. The support for other indications is weaker, but rapidly increasing.

Anti-Müllerian hormone levels in salpingectomized compared with nonsalpingectomized women with tubal factor infertility and women with unexplained infertility.

OBJECTIVE: To investigate the consequence of salpingectomy on ovarian reserve by measuring anti-Müllerian hormone (AMH) levels before in vitro fertilization (IVF) treatment in salpingectomized women compared with nonsalpingectomized women with tubal factor infertility, women with unexplained infertility and fertile control women, and to evaluate whether AMH levels could predict IVF outcome. DESIGN: Cross-sectional study extended from a previous prospective study. SETTING: Four university fertility clinics. PATIENTS: Seventy-one women with infertility and 21 fertile controls. INTERVENTIONS: Blood sampling and IVF and embryo transfer in the following cycle. MAIN OUTCOME MEASURE: Serum AMH levels and oocytes retrieved. RESULTS: Anti-Müllerian hormone levels were significantly lower in the salpingectomy infertility group (median 16.1, range 5.2-54 pmol/L) compared with the nonsalpingectomy tubal factor infertility group (median 23.4, range 3.5-50 pmol/L; p = 0.04). In all groups, AMH levels correlated positively with the number of oocytes retrieved. AMH predicted poor response (five or fewer oocytes) with a sensitivity and specificity of 90% and 70%, at a 19 pmol/L cut-off value. CONCLUSION: Serum AMH levels were lower in salpingectomized women compared with women with tubal factor infertility and preserved Fallopian tubes, indicating that ovarian reserve might be affected by tubal surgery. Furthermore, serum AMH levels could predict a poor oocyte response (five or fewer oocytes) in the study group of infertile women.

The role of anti-Müllerian hormone in female fertility and infertility - an overview.

Anti-Müllerian hormone (AMH) plasma levels reflect the continuous non-cyclic growth of small follicles, thereby mirroring the size of the resting primordial follicle pool and thus acting as a useful marker of ovarian reserve. Anti-Müllerian hormone seems to be the best endocrine marker for assessing the age-related decline of the ovarian pool in healthy women; thus, it has a potential ability to predict future reproductive lifespan. The most established role for AMH measurements is before in vitro fertilization is initiated, because AMH can be predictive of the ovarian response, namely poor and hyper-responses. However, recent research has also highlighted the use of AMH in a variety of ovarian pathological conditions, including polycystic ovary syndrome, granulosa cell tumors and premature ovarian failure. A new commercial enzyme-linked immunosorbent assay for measuring AMH levels has been developed, making results from different studies more comparable. Nevertheless, widespread clinical application awaits an international standard for AMH, so that results using future assays can be reliably compared.

A severe valproate overdose with complete recovery in a newborn.

Valproate overdose, extensively described in adults and older children, has been reported in only 1 newborn: a 26-day-old female who developed a severe cerebral edema leading to a fatal outcome. Therefore, the consequences of valproate overdose are largely unknown in the neonatal period. Here, we present the clinical evolution of a 6-day-old newborn who developed hyperammonemic encephalopathy after the accidental administration of 310 mg/kg of oral valproate in a single dose. Despite the very high valproate and blood ammonia levels, he did not develop life-threatening complications and he completely recovered without sequels. His brain magnetic resonance imaging showed symmetric focal T1 prolonged signals in both globi pallidi that completely resolved over time, a neuroimaging pattern that was not previously described in valproate overdose. Our case report suggests that valproate overdose in newborns can be completely reversible even when the valproate and ammonium blood levels are very high.