Molly B. Moravek

Thiazolidinediones as Therapy for Endometriosis: A Case Series

Background: Current medical therapies for endometriosis result in delayed conception and have not been shown to provide any fertile benefit subsequent to treatment. Thiazolidinediones (TZDs) do not impede conception and have been shown to reduce endometriotic lesions in animal models; however, no studies have been performed in humans. The aim of this study was to provide preliminary data about the effectiveness of a TZD in treating endometriosis-related pain. Methods: Case series of women with endometriosis recruited from the University of Michigan as part of an open-label prospective phase 2a clinical trial. Participants were given rosiglitazone, 4 mg daily, for 6 months. Subjective endometriosis symptoms were assessed using a modified Biberoglu and Behrman symptom severity scale and the McGill pain questionnaire. Results: Two of the 3 patients exhibited improvement in severity of symptoms and pain levels with a concurrent decrease in pain medication, while 1 experienced no change. Rosiglitazone was well tolerated by all patients. Conclusions: Combined with data gathered from studies in rats and nonhuman primates, the results from this study offer positive justification for using TZDs as a well-tolerated treatment for endometriosis that can address pain without impeding ovulation and without the need for add-back therapy.

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.

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.

Experience of symptoms, sexual function, and attitudes toward counseling of women newly diagnosed with vulvodynia.

Objective This study aimed to assess health beliefs and behaviors, experience of pain, coping mechanisms, sexual function, and attitudes toward counseling of patients newly diagnosed with vulvodynia. Materials and Methods Participants were enrolled from all newly diagnosed vulvodynia patients seen at the University of Michigan Vulvar Disease Clinic at Chelsea. Participants completed a questionnaire assessing perceptions and beliefs about their vulvodynia, coping ability, sexual function, and interest in counseling. Results Thirty-one women were enrolled, ranging in age from 21 to 81 years; 68% had current partners. On a scale of 1 to 10 (low to high), participants rated their symptoms as severe—(mean [SD] = 7.42 [1.50]), perceived little control over symptoms (2.61 [2.64]); were very concerned about symptoms (8.77 [1.73]); and were very emotionally affected by their disorder (7.00 [2.82]). During the previous 4 weeks, 52% reported low to no sexual desire; 71% reported being dissatisfied with their overall sex life; 26% were not comfortable saying no to partner sex; 23% to 36% did not attempt penetration; and for 36%, their pain was rated as high or very high. Sixty-one percent of women indicated that they would consider counseling for coping with vulvar pain. In addition, 29% (9/31) said they “would” and 48% (15/31) said they “maybe would” consider seeing a sex therapist for their vulvar pain. Conclusions Women with newly diagnosed vulvodynia report substantial impact of vulvar pain but feel little control over symptoms. Sexual desire and sexual satisfaction are low. Most of the respondents would consider counseling to help address these issues.

Oncofertility program implementation increases access to fertility preservation options and assisted reproductive procedures for breast cancer patients

Breast cancer treatment can cause premature ovarian failure, yet the majority of young cancer patients do not receive adequate education about treatment effects before initiating chemotherapy. We studied the impact of an oncofertility program on access to fertility preservation.

Public perceptions of endometriosis: perspectives from both genders

Objective. Many women with endometriosis experience significant delay between the onset of symptoms and definitive diagnosis. Much is published on physician awareness of endometriosis and on the experiences of women with the condition. There is a paucity of data, however, surrounding perceptions of endometriosis in the general population. This study aims to assess knowledge of endometriosis among individuals of both genders. Design. Survey study. Setting. Family waiting room of a large university hospital. Population. A total of 543 men and women. Methods. Surveys were distributed to men and women over the age of 18 in the family waiting room of a large university hospital. Main outcome measures. A series of questions regarding the etiology, symptoms, and treatments for endometriosis were combined into a composite knowledge score. Results. Knowledge of endometriosis was positively correlated with female gender, education level, regular health care, and exposure to individuals with the disease. Women diagnosed with endometriosis were more likely to have discussed symptoms of the condition with their physicians than women without the diagnosis. Conclusions. Individuals of both genders have limited knowledge of the signs and symptoms of endometriosis, which may contribute to the delay in diagnosis of the condition.

The impact of fertility preservation on treatment delay and progression-free survival in women with lymphoma: a single-centre experience.

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HCG-mediated activation of mTORC1 signaling plays a crucial role in steroidogenesis in human granulosa lutein cells

Luteinizing hormone/human chorionic gonadotropin stimulates progesterone biosynthesis in the corpus luteum by activating cyclic adenosine monophosphate/protein kinase A cascade. Recent studies have shown that cyclic adenosine monophosphate-mediated activation of protein kinase A interacts with the mammalian target of rapamycin signaling pathways. Furthermore, the use of mammalian target of rapamycin inhibitors for immunosuppression in transplant patients has shown adverse effects in reproductive functions. This study examined whether the mammalian target of rapamycin pathway plays any role in luteinizing hormone-mediated regulation of progesterone production. Human granulosa lutein cells were isolated from follicular aspirates of women undergoing in vitro fertilization. Cells were cultured for 72 h and treated with human chorionic gonadotropin (50 ng/ml) for different time periods with or without pretreatment with mammalian target of rapamycin complex 1 inhibitor, rapamycin, (20 nM) for 1 h. Expression of steroidogenic enzymes, including steroidogenic acute regulatory protein, cholesterol side chain cleavage enzyme, and 3β-hydroxysteroid dehydrogenase type 1 messenger RNA, were examined by real-time polymerase chain reaction after 6 h of human chorionic gonadotropin treatment. Expressions of phospho-ribosomal protein S6 kinase and cholesterol side chain cleavage enzyme were analyzed after 15 min and 24 h of human chorionic gonadotropin treatment, respectively. Progesterone production was analyzed by an enzyme immunoassay kit after human chorionic gonadotropin (50 ng/ml) or forskolin (10 μM) treatment for 24 h. Treatment with human chorionic gonadotropin increased the expression of downstream targets of mammalian target of rapamycin complex 1, as well as cholesterol side chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase type 1 and steroidogenic acute regulatory protein messenger RNAs. These increases were inhibited by rapamycin pretreatment. Increased progesterone production in response to treatment with human chorionic gonadotropin or forskolin was also blocked by rapamycin pretreatment. Our findings support a role for mammalian target of rapamycin complex 1 in regulating steroidogenesis in human granulosa lutein cells.

Oncofertility Options for Young Women With Breast Cancer

Breast cancer is the most common cancer diagnosed in women in the United States. Approximately 12% of breast cancers are diagnosed in women younger than 44 years of age. The 5-year relative survival rate for early-stage breast cancer is approximately 98%, yet younger women, diagnosed before age 40, have a 5-year relative survival rate closer to 85%. Emerging treatments for breast cancer continue to result in improved outcomes, although some of these successful therapies have comorbidities, including long-term effects on the ovaries, resulting in premature ovarian failure and reduced fertility. The concept of fertility preservation, or oncofertility, was first proposed with the goal of improving posttreatment reproductive outcomes for young patients diagnosed with cancer. The interdisciplinary Oncofertility Consortium of physicians and scientists was consequently created and supported by the National Institute of Health. Currently, several societies including the American Society of Clinical Oncology (ASCO), the American Society of Reproductive Medicine (ASRM), and the National Comprehensive Cancer Network (NCCN) have guidelines advocating for counseling of young cancer patients regarding fertility preservation before the initiation of treatment. Understanding ovarian biology in the context of a cancer diagnosis in young women and the existing and emerging options to protect hormonal and reproductive health is of importance to the patients and is reviewed in this chapter.