Senait Fisseha

Adjunctive GnRH-a treatment attenuates depletion of ovarian reserve associated with cyclophosphamide therapy in premenopausal SLE patients

Background: We measured antimullerian hormone (AMH), a marker of ovarian reserve, in women with lupus treated with cyclophosphamide (CYC) (group I), CYC plus gonadotropin-releasing hormone agonist (GnRH-a) (group II) or neither (group III). We hypothesized that AMH would be diminished in women exposed to CYC versus women receiving adjunctive GnRH-a treatment or no CYC exposure. Methods: Forty-eight premenopausal lupus patients were retrospectively divided into three treatment groups: CYC alone (group I, n = 11), CYC + GnRH-a (group II, n = 10) and neither (group III, n = 27). Serum AMH levels between groups were compared using a nonparametric test (Wilcoxon rank-sum). Multiple linear regression adjusting for age was performed. Results: AMH (ng/mL) levels at the last collection were significantly lower in group I versus group III (mean ± SD: 0.18 ± 0.20 group I vs 1.33 ± 1.59 group III; p = 0.015), and versus group II (mean ± SD: 0.86 ± 1.06; p = 0.018). When centered on age 30 years, average AMH levels for group I, group II and group III were 0.20, 0.44 and 1.00, respectively. When adjusted for age, AMH between all groups was significantly different (p<0.0001). Conclusion: Posttreatment AMH levels were significantly higher among patients receiving CYC + GnRH-a compared to CYC alone, suggesting that GnRH-a coadministration mitigates CYC-induced ovarian injury.

A systematic review of the evidence for complementary and alternative medicine in infertility

The use of complementary and alternative medicine (CAM) by patients and physicians has increased markedly in recent years. Many case reports, case series, and uncontrolled trials of varying quality have been completed; however, there is now a slowly increasing number of randomized controlled trials (RCTs) examining the use of CAM.

Medical, ethical, and legal considerations in fertility preservation

The past 2 decades have seen a significant rise in cancer survival rates, and an increasing proportion of survivors at reproductive age are interested in childbearing. Although assisted reproduction provides physicians with an array of potential possibilities to help patients whose fertility is compromised by cancer treatment, there is still a dearth of regulation regarding the application of this technology. The present paper reviews the current options for fertility preservation, with a particular focus on the legal and ethical challenges that confront providers of this type of care.

Assessment of multiple intrauterine gestations from ovarian stimulation (AMIGOS) trial: baseline characteristics

OBJECTIVE To identify baseline characteristics of women with unexplained infertility to determine whether treatment with an aromatase inhibitor will result in a lower rate of multiple gestations than current standard ovulation induction medications. DESIGN Randomized, prospective clinical trial. SETTING Multicenter university-based clinical practices. PATIENT(S) A total of 900 couples with unexplained infertility. INTERVENTION(S) Collection of baseline demographics, blood samples, and ultrasonographic assessments. MAIN OUTCOME MEASURE(S) Demographic, laboratory, imaging, and survey characteristics. RESULT(S) Demographic characteristics of women receiving clomiphene citrate (CC), letrozole, or gonadotropins for ovarian stimulation were very consistent. Their mean age was 32.2 ± 4.4 years and infertility duration was 34.7 ± 25.7 months, with 59% primary infertility. More than one-third of the women were current or past smokers. The mean body mass index (BMI) was 27 and mean antimüllerian hormone level was 2.6; only 11 women (1.3%) had antral follicle counts of <5. Similar observations were identified for hormonal profiles, ultrasound characterization of the ovaries, semen parameters, and quality of life assessments in both male and female partners. CONCLUSION(S) The cause of infertility in the couples recruited to this treatment trial is elusive, as the women were regularly ovulating and had evidence of good ovarian reserve both by basal FSH, antimüllerian hormone levels, and antral follicle counts; the male partners had normal semen parameters. The three treatment groups have common baseline characteristics, thereby providing comparable patient populations for testing the hypothesis that use of letrozole for ovarian stimulation can reduce the rates of multiples from that observed with gonadotropin and CC treatment. CLINICAL TRIAL REGISTRATION NUMBER NCT 01044862.

Ovarian Damage During Chemotherapy in Autoimmune Diseases: Broad Health Implications beyond Fertility

Women with autoimmune diseases such as lupus, scleroderma, and vasculitis receiving cyclophosphamide for severe disease manifestations risk primary ovarian insufficiency (POI) due to gonadotoxicity of this therapy. In addition to loss of reproductive potential, POI is associated with increased risk of morbidity and mortality. Practitioners caring for women requiring gonadotoxic therapies should be familiar with long-term health implications of POI and strategies for ovarian preservation. Accumulating evidence supports the effectiveness of adjunctive gonadotropin releasing hormone analog (GnRH-a) for ovarian protection during gonadotoxic therapy in cancer and autoimmune populations. GnRH-a is less costly and invasive than assisted reproductive technologies used for achievement of future pregnancies, but is not Food and Drug Administration approved for ovarian preservation. This review focuses on POI comorbidities and strategies for mitigation of related sequelae, which can accumulate over decades of hypoesteogenism. These issues are arguably more pronounced for women with chronic autoimmune diseases, in whom superimposed POI further heightens risks of cardiovascular disease and osteoporosis. Therefore, even if future pregnancy is not desired, ovarian protection during gonadotoxic therapy should be a major goal of disease management.

Dipeptide forms of glycine support mouse preimplantation embryo development in vitro and provide protection against high media osmolality.

PurposeTo examine potential benefits of dipeptide forms of amino acids for embryo culture by determining ability of dipeptide glycine forms to support embryo development, act as osmolytes, and reduce ammonia production.MethodsFrozen thawed 1-cell mouse embryos were cultured in media with varying osmolality with glycine and dipeptide forms of glycine and development assessed. Ammonia levels were measured in various media.ResultsDipeptide forms of glycine, alanyl- and glycyl-glycine, can support mouse embryo development in vitro. Additionally, dipeptide glycine can act as an organic osmolyte in developing embryos, permitting blastocyst formation in high osmolality media. Interestingly, as evidenced by decreased embryo development, dipeptides are not as efficient as osmolytes as their constituent individual amino acids. Dipeptide glycine produced less ammonia than glycine.ConclusionThough dipeptides can provide osmoregulation in preimplantation embryos, efficacy may be lower than individual amino acids. The mechanism by which embryos transport and utilize dipeptide amino acids remains to be identified.

Physician and patient use of and attitudes toward complementary and alternative medicine in the treatment of infertility.

To determine use of and attitudes toward complementary and alternative medicine (CAM) among infertility patients and subspecialty physicians.

Inhibitory effect of valproic acid on ovarian androgen biosynthesis in rat theca-interstitial cells

The objective of the study was to evaluate the effect of valproic acid (VPA) on ovarian androgen biosynthesis in primary cultures of theca-interstitial (T-I) cells isolated from rat ovaries. Ovarian T-I cells were cultured with VPA in the presence or absence of hCG. VPA did not increase basal or hCG-stimulated androgen synthesis when added to primary cultures of T-I cells. However, the addition of VPA caused a marked concentration-dependent inhibitory effect on hCG-stimulated androstendione synthesis. Treatment of T-I cells with 8-Bromo-cAMP resulted in a marked increase in the production of androstenedione, and VPA inhibited this stimulatory effect, suggesting that the mechanism of VPA’s inhibitory effect on androstenedione production occurs at a step after second messenger activation. Treatment of T-I cells with hCG resulted in a significant increase in the mRNA expression of steroidogenic enzymes CYP17A1 and 17β-hydroxysteroid dehydrogenase. Addition of VPA sharply blunted the stimulatory effect of hCG, reducing the mRNA expression of the steroidogenic enzymes to basal levels. In conclusion, VPA exerts an inhibitory effect on hCG-stimulated androgen synthesis in rat T-I cells.

The relationship between facility delivery and infant immunization in Ethiopia

To determine whether facility delivery is related to compliance with recommended infant immunizations, particularly those that occur weeks or months after delivery.

Major depression, antidepressant use, and male and female fertility

OBJECTIVE To determine if maternal major depression (MD), antidepressant use, or paternal MD are associated with pregnancy outcomes after non-IVF fertility treatments. DESIGN Cohort study. SETTING Clinics. PATIENT(S) Participants in two randomized trials: PPCOS II (clomiphene citrate versus letrozole for polycystic ovary syndrome), and AMIGOS (gonadotropins versus clomiphene citrate versus letrozole for unexplained infertility). INTERVENTION(S) Female and male partners completed the Patient Health Questionnaire (PHQ-9). Female medication use was collected. PHQ-9 score ≥10 was used to define currently active MD. MAIN OUTCOME MEASURE(S) Primary outcome: live birth. SECONDARY OUTCOMES pregnancy, first-trimester miscarriage. Poisson regression models were used to determine relative risks after adjusting for age, race, income, months trying to conceive, smoking, and study (PPCOS II versus AMIGOS). RESULT(S) Data for 1,650 women and 1,608 men were included. Among women not using an antidepressant, the presence of currently active MD was not associated with poorer fertility outcomes (live birth, miscarriage), but rather was associated with a slightly increased likelihood of pregnancy. Maternal antidepressant use (n = 90) was associated with increased risk of miscarriage, and male partners with currently active MD were less likely to achieve conception. CONCLUSION(S) Currently active MD in the female partner does not negatively affect non-IVF treatment outcomes; however, currently active MD in the male partner may lower the likelihood of pregnancy. Maternal antidepressant use is associated with first-trimester pregnancy loss, which may depend upon the type of antidepressant. CLINICAL TRIAL REGISTRATION NUMBERS NCT00719186 and NCT01044862.