In Vitro Fertilization for Polycystic Ovarian Syndrome.

In vitro fertilization is indicated for infertile women with polycystic ovarian syndrome (PCOS) after unsuccessful treatment with ovulation induction agents or in women deemed high-risk of multiple gestations who are ideal candidates for single embryo transfers. PCOS patients are at increased risk of ovarian hyperstimulation syndrome; therefore, attention should be made in the choice of in vitro fertilization treatment protocol, dose of gonadotropin utilized, and regimen to achieve final oocyte maturation. Adopting these strategies in addition to close monitoring may significantly reduce the ovarian hyperstimulation syndrome risk. Future developments may improve pregnancy outcomes and decrease complications in PCOS women undergoing fertility treatment.

Polycystic Ovarian Syndrome and Fertility.

Polycystic ovary syndrome (PCOS) is a common endocrinopathy that has been associated with impaired fertility. This chapter reviews the underlying pathophysiology of PCOS and the associated fertility barriers of the condition. Psychologic concerns, hypothalamic-pituitary, ovarian, and mitochondria dysfunction, obesity, and the role of vitamin D in PCOS are considered with respect to fertility. Lastly, pregnancy risk factors associated with PCOS are also reviewed.

Pharmacologic Treatments for PCOS Patients.

Polycystic ovarian syndrome is the most common endocrinopathy in reproductive-aged women and has a vast array of clinical manifestations. Common clinical presentations of the disorder include anovulatory infertility, menstrual disorders, cutaneous symptoms secondary to androgen excess, metabolic abnormalities and mental health issues. If the condition is left unaddressed or inadequately treated, long-term sequelae such as endometrial hyperplasia, diabetes mellitus and dyslipidemia may ensue, therefore it is imperative for clinicians to address each component of the syndrome. When initial lifestyle changes and dietary modifications do not suffice or fail, pharmacologic therapy should be considered, and when deemed appropriate treatment should be initiated. This review describes the pharmacologic options available to combat the various sequelae commonly seen in women with polycystic ovarian syndrome.

A Case of Intertwin Membrane Hemorrhage with Spontaneous Resolution.

Vaginal bleeding during pregnancy places women at increased risk of spontaneous abortion. Etiologies for threatened and spontaneous abortions have been well studied, but there is little information on intertwin membrane hemorrhage. We present a patient with a multiple gestation pregnancy who experienced first trimester vaginal bleeding with visualization and subsequent rapid resolution of an intertwin membrane hemorrhage. The patient had an otherwise normal pregnancy until the third trimester when she developed preeclampsia with severe features and elected for a primary cesarean section at 35 + 5 weeks. The implications of an intertwin membrane hemorrhage are not well understood, although there could be a possible correlation between the hemorrhage and the ultimate progression to preeclampsia with severe features. Despite the final diagnosis, the patient did not have any noticeable complications due to the hemorrhage both when it was discovered and in the weeks following its discovery.

Assisted Reproductive Technology and the Reproductive Endocrinology and Infertility Specialist in the U.S. Military.

The U.S. military mirrors the U.S. population given the diverse ethnic and cultural backgrounds of the service members. Active-duty military members, veterans, and Department of Defense beneficiaries can be negatively impacted by infertility.

Premature Ovarian Insufficiency - an update on recent advances in understanding and management.

Premature ovarian insufficiency is a complex and relatively poorly understood entity with a myriad of etiologies and multisystem sequelae that stem from premature deprivation of ovarian sex hormones. Timely diagnosis with a clear understanding of the various comorbidities that can arise from estrogen deficiency is vital to appropriately counsel and treat these patients. Prompt initiation of hormone therapy is critical to control the unsolicited menopausal symptoms that many women experience and to prevent long-term health complications. Despite ongoing efforts at improving our understanding of the mechanisms involved, any advancement in the field in recent decades has been modest at best and researchers remain thwarted by the complexity and heterogeneity of the underpinnings of this entity. In contrast, the practice of clinical medicine has made meaningful strides in providing assurance to the women with premature ovarian insufficiency that their quality of life as well as long-term health can be optimized through timely intervention. Ongoing research is clearly needed to allow pre-emptive identification of the at-risk population and to identify mechanisms that if addressed in a timely manner, can prolong ovarian function and physiology.

Premature Menopause.

A heterogeneous disorder, premature menopause is not an uncommon entity, affecting approximately 1% of women younger than 40 years. Multisystem implications are recognized as sequelae to the premature deprivation of ovarian steroids, posing unique health-related challenges in this population. An integrated management approach that addresses both the physical and psychological health concerns and the overall well-being of this relatively chronologically young population is paramount.

Is the fertility treatment itself a risk factor for early pregnancy loss?

PURPOSE OF REVIEW: With the recent advancements in reproductive medicine, many infertile couples now have the opportunity to conceive their own biological children. Although some medication protocols, such as clomiphene citrate, have been utilized for decades, other treatment modalities have evolved over the recent years. It therefore becomes imperative to assess the outcomes of these modalities and be critical regarding their safety. Pregnancy loss is one outcome that can affect many couples who conceive both spontaneously and with assistance via fertility treatment. In this review, several of the most commonly used fertility treatments will be discussed and the impact, if any, they may have in early pregnancy loss will be addressed. RECENT FINDINGS: Current data do not support that notion that infertility treatments or assisted reproductive techniques contribute to early pregnancy loss. However, more studies are needed to eliminate the confounding variables that make data interpretation difficult to generalize to the infertile population. SUMMARY: An early pregnancy loss can cause emotional distress and grief, particularly for couples already dealing with an infertility diagnosis. Therefore, knowledge regarding the relationship between infertility and early pregnancy loss is vital in order to properly counsel the couple prior to starting treatment.

Human embryonic poly(A)-binding protein (EPAB) alternative splicing is differentially regulated in human oocytes and embryos.

Oocyte maturation is associated with suppression of transcriptional activity. Consequently, gene expression during oocyte maturation, fertilization and early embryo development, until zygotic genome activation (ZGA) is primarily regulated by translational activation of maternally derived mRNAs. Embryonic poly(A)-binding protein (EPAB) is the predominant poly(A)-binding protein in Xenopus, mouse and human oocytes and early embryos prior to ZGA. EPAB plays a key role in polyadenylation-dependent translational activation of mRNAs by stabilizing polyadenylated mRNAs and by stimulating their translation. Epab-knockout female mice are sterile, fail to generate mature oocytes and display impaired cumulus expansion and ovulation. Consistent with its role during gametogenesis and early embryo development, Xenopus and mouse Epab mRNA is expressed exclusively in oocytes and early embryos, and is undetectable following ZGA or in somatic tissues. Herein, we demonstrate that although EPAB is expressed in human somatic tissues, its transcripts largely consist of an alternatively spliced form lacking the first 58 bp of exon 8, which leads to the formation of a premature stop codon 6 amino acids downstream on exon 8, and omission of the functionally critical poly(A)-binding domain. Moreover, 8-cell and blastocyst stage human embryos also express only the alternatively spliced form of EPAB. On the other hand, the full-length form of EPAB mRNA is exclusively expressed in oocytes. In conclusion, in contrast with the transcriptional regulation in Xenopus and mouse, oocyte- and early embryo-specific expression of EPAB in human is regulated by a post-transcriptional mechanism.

Characterization of the gonadotropin releasing hormone receptor (GnRHR) expression and activity in the female mouse ovary.

GnRH agonists (GnRHa) are increasingly used for fertility preservation in women undergoing gonadotoxic chemotherapy. However, the protective mechanisms of action for these compounds have not yet been elucidated. In this study, we aimed to determine whether GnRHa have a direct effect on ovarian granulosa cells. GnRH receptor (GnRHR) expression was determined in mouse somatic and gonadal tissues including granulosa/cumulus cells and oocytes using quantitative RT-PCR and immunohistochemistry. Granulosa cells were isolated from mouse ovaries primed with pregnant mare serum gonadotropin. Response to GnRHa in cultured granulosa cells was assessed by determining the increase of intracellular cAMP and by assessing phosphorylation of downstream mediators of GnRH signaling: ERK and p38. To measure intracellular cAMP in our system, the cells were transfected with a cAMP-responsive luciferase reporter plasmid and stimulated with GnRHa. For all experiments, pituitary tissue and/or the αT3-1 mouse pituitary cell line were used as controls. GnRHR mRNA and protein were detected in mouse ovaries, granulosa/cumulus cells, and oocytes. After GnRHa stimulation at various time intervals, we were unable to detect a cAMP increase or activation of the ERK or p38 signaling pathway in cultured primary mouse granulosa cells, whereas activation was detected in the control αT3-1 mouse pituitary cells. In this study, we have not detected activation of the canonical GnRH signaling pathways in mouse ovarian somatic cells. Our findings suggest that the mechanism of action of GnRHa in the ovary is either below the detection level of our experimental design or is different from that in the pituitary.

Cumulus and granulosa cell markers of oocyte and embryo quality.

Lack of an objective, accurate, and noninvasive embryo assessment strategy remains one of the major challenges encountered in in vitro fertilization. Cumulus and mural granulosa cells reflect the characteristics of the oocyte, providing a noninvasive means to assess oocyte quality. Specifically, transcriptomic profiling of follicular cells may help identify biomarkers of oocyte and embryo competence. Current transcriptomics technologies include quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) for analysis of individual genes and microarrays and high-throughput deep sequencing for whole genome expression profiling. Recently, using qRT-PCR and microarray technologies, a multitude of studies correlated changes in cumulus or granulosa cell gene expression with clinically relevant outcome parameters, including in vitro embryo development and pregnancy. While the initial findings are promising, a clinical benefit from the use of identified biomarker genes remains to be demonstrated in randomized controlled trials.

Acute portal vein thrombosis complicating in vitro fertilization.

OBJECTIVE: To describe a case of acute portal vein thrombosis after IVF treatment. DESIGN: Case report. SETTING: University teaching hospital. PATIENT(S): A 39-year-old woman experienced worsening, right upper quadrant pain several days after oocyte retrieval; ET was withheld. Imaging studies revealed acute portal vein thrombosis with extension into the splenic and superior mesenteric veins. INTERVENTION(S): Therapeutic anticoagulation; no ET was performed. MAIN OUTCOME MEASURE(S): Improvement in symptoms, accurate diagnosis of condition. RESULT(S): Decreased size of portal vein thrombosis and partial vessel recanalization. CONCLUSION(S): Thromboembolic events are a rare complication of assisted reproductive technology (ART). In women who present with upper abdominal pain during ART, portal vein thrombosis should be considered in the differential diagnosis.

Relevance of vitamin D in reproduction.

The steroid hormone vitamin D is historically recognized for its relevance to bone health and calcium homeostasis. Recent years have witnessed a shift in focus to non-skeletal benefits of vitamin D; in this latter context, an accruing body of literature attests to a relevance of vitamin D to reproductive physiology. This article reviews the existing data about the diverse and previously underappreciated roles for vitamin D in reproductive health. A large body of available literature suggests that vitamin D deficiency may be detrimental to reproductive biology. However, given that our appreciation of vitamin D's role in reproductive physiology is almost entirely shaped by 'associative' studies and that data based on prospective interventional trials are limited, these concepts remain predominantly conjectural. Exact mechanisms whereby vitamin D may participate in the regulation of reproductive physiology remain far from clear. This review underscores a need for appropriately designed intervention trials to address the existing knowledge gaps and to delineate the specific roles of vitamin D signaling in reproductive biology.

Benign gynecologic conditions.

Benign gynecologic conditions constitute the majority of the general gynecologist's practice. Along with health maintenance examinations, contraceptive management, family planning issues, and concerns about incontinence, the gynecologic conditions for which patients commonly present include adnexal masses, leiomyomata, endometriosis, and pelvic inflammatory disease. This article addresses each of these last four entities and incorporates a discussion of their etiologies, clinical presentations, keys to diagnosis, and the various treatment options available.

Angiogenic network formation in the developing vertebrate trunk.

We have used time-lapse multiphoton microscopy of living Tg(fli1:EGFP)y1 zebrafish embryos to examine how a patterned, functional network of angiogenic blood vessels is generated in the early vertebrate trunk. Angiogenic vascular sprouts emerge from the longitudinal trunk axial vessels (the dorsal aorta and posterior cardinal vein) in two spatially and temporally distinct steps. Dorsal aorta-derived sprouts form an initial primary network of vascular segments, followed by emergence of vein-derived secondary vascular sprouts that interact and interconnect dynamically with the primary network to initiate vascular flow. Using transgenic silent heart mutant embryos, we show that the gross anatomical patterning of this network of vessels does not require blood circulation. However, our results suggest that circulatory flow dynamics play an important role in helping to determine the pattern of interconnections between the primary network and secondary sprouts, and thus the final arterial or venous identity of the vessels in the functional network. We discuss a model to explain our results combining genetic programming of overall vascular architecture with hemodynamic determination of circulatory flow patterns.