Hyacinth Browne

The pathophysiology of ovarian hyperstimulation syndrome: an unrecognized compartment syndrome

OBJECTIVE To compare and contrast the pathophysiology of ovarian hyperstimualtion syndrome (OHSS) with known syndromes of increased intraabdominal pressure (IAP), and to explore the relationship of increased IAP with symptom severity in OHSS. DESIGN Literature review. MAIN OUTCOME MEASURE(S) Correlation of OHSS symptoms with IAP; effects of paracentesis on IAP in patients with OHSS. SETTING Academic Research Institution. INTERVENTION(S) None. RESULT(S) OHSS involves a rapid accumulation of volume (from 1.5-17 liters) in the peritoneal cavity that can lead to organ dysfunction, including respiratory impairment and oliguria. In published reports of 20 moderate-to-severe OHSS patients in whom IAP was measured, IAP was found to be elevated to a pathologic range. The increased IAP indicates that OHSS may be considered a compartment syndrome and meets criteria for abdominal compartment syndrome in advanced cases. For this reason, management of OHSS should include reduction of pressure by paracentesis to avoid morbidity and syndrome progression. In addition, measurement of IAP may help to classify the stage of OHSS. CONCLUSION(S) IAP was found to be elevated in the few cases of OHSS in which it was measured, substantiating the conclusion that OHSS may be considered a compartment syndrome. An understanding of the pathophysiology of increased intrabdominal pressure is useful in the management of OHSS.

Assessment of ovarian function with anti-Müllerian hormone in systemic lupus erythematosus patients undergoing hematopoietic stem cell transplant

In this small pilot study, anti-Müllerian hormone (AMH) levels in women undergoing chemotherapy and hematopoietic stem cell transplantation facilitated earlier identification of impaired ovarian reserve compared with FSH and the resumption of menses. Larger studies are needed to accurately assess the clinical significance of AMH levels in the prediction of long-term reproductive outcomes in reproductive-age transplant patients with our current conditioning regimen.

Is anti-Müllerian hormone a marker of acute cyclophosphamide-induced ovarian follicular destruction in mice pretreated with cetrorelix?

OBJECTIVE To define whether anti-Müllerian hormone (AMH) may be a marker of acute cyclophosphamide (CTX)-induced germ cell destruction in mice pretreated with the GnRH antagonist, cetrorelix. DESIGN Controlled, experimental study. SETTING Research laboratory in a federal research facility. ANIMAL(S) Balb/c female mice (6 weeks old). INTERVENTION(S) Mice were treated with GnRH antagonist (cetrorelix) or saline for 15 days followed by 75 mg/kg or 100 mg/kg of CTX or saline control on day 9. MAIN OUTCOME MEASURE(S) Number of primordial follicles (PMF), DNA damage, AMH protein expression, and AMH serum levels. RESULT(S) Ovaries in mice pretreated with cetrorelix had significantly more PMFs and reduced DNA damage compared with those exposed to CTX alone. Immunohistochemical staining for AMH expression and serum AMH levels did not differ significantly between treatment groups. CONCLUSION(S) Cetrorelix protected PMFs and reduced DNA damage in follicles of mice treated with CTX, but AMH levels in tissue and serum did not correlate with germ cell destruction. Further research is needed to determine the mechanism responsible for the protective effects on PMF counts observed with cetrorelix.

Ethical and psychological considerations in fertility preservation counseling.

The retrospective analysis by Jenninga et al of their 5-year clinical experience with fertility preservation therapies and the ethical considerations associated with these therapies is timely and relevant. Over the past 25 years, the 5-year relative survival rate for all cancers combined improved from 56% to 64% in women.1 Furthermore, cure rates for 2% of all malignant diseases occurring during childhood and adolescence can exceed 90%.2–4 By 2010, 1 of 250 adults will be childhood cancer survivors.4–6 As the life expectancy of cancer survivors improves, the effect of cancer treatment on fertility has become paramount. With increasing survival rates, physicians should be encouraged to discuss fertility preservation options with their patients at the earliest opportunity.7 The ethical considerations and dilemmas associated with fertility preservation therapies must be addressed as this field continues to evolve. The use of fertility preservation therapies should take into consideration the age and marital status of the patient, religious or ethical objections to embryo freezing, the type of malignancy and treatment, the risk-tobenefit ratio of delaying treatment, and the patient’s prognosis after treatment.1,7 Furthermore, greater awareness about the psychosocial and psychosexual morbidity associated with cancer-related infertility and cancer patients’ attitudes, emotions, and choices with regard to having children is needed.8 The loss of fertility not only equates to an inability to bear children, but can also affect one’s sexuality, identity and role expectations, and the pursuit of intimacy and marriage.9 Currently, the choices for preserving fertility in chemotherapy and radiation patients are limited. Down-regulation of the hypothalamic-pituitary-ovarian axis with hormonal agents, such as GnRH analogues, has been used in reproductive-aged patients receiving chemotherapy. In vitro fertilization with embryo cyropreservation, ovarian transposition, and techniques for gamete preservation such as sperm cryopreservation, oocyte, and ovarian tissue cryopreservation are all surgical techniques to preserve fertility though with limited success. Sperm and embryo cryopreservation are the only clinically well-established procedures that have been shown to be effective fertility preservation therapies. Sperm cryopreservation should be offered to all men undergoing cancer treatment, whereas embryo cryopreservation should be considered first-line therapy for fertility preservation in women who have a partner and enough time to undergo at least one in vitro fertilization cycle.1 Although these techniques are not feasible for prepubertal girls, women without a partner, and men with low sperm counts, they are associated with higher pregnancy rates compared with oocyte and ovarian tissue cryopreservation. These latter techniques are still investigational and all have demonstrated variable success. They should only be performed as experimental procedures under IRB approved protocols and at centers with the necessary expertise.1,7,10 Despite the advances that have been made in this field, patient counseling about fertility preservation is limited. In the present study by Jenninga et al, they showed that only 2% of patients in their study, who were at risk for developing premature ovarian failure, were referred to their center to undergo fertility preservation therapy. This is despite the fact that more women in the Netherlands, according to the Dutch Cancer Registry, were reported to have an eightfold risk of developing premature ovarian failure. Underuse of these techniques may be due to a lack of timely discussions7 between physicians and patients about treatment-induced infertility.11,12 Prior studies13–17 have shown that health care professionals are inconsistent with their discussions involving decisions about fertility preservation despite being aware of the adverse affects of cancer treatment on fertility. This may be attributed to decreased knowledge about the safety, efficacy, and experimental advances in assisted reproductive technology.13,15 Practitioners have also expressed difficulty in finding facilities and reproductive specialists who perform these procedures.13,15 Schover et al,12 in a recent survey, showed that young male cancer survivors who desired future children lacked timely information about sperm cryopreservation. They reported this to be the most common reason for not banking sperm. Only 60% of these cancer survivors recalled a health provider having discussed fertility before cancer treatment began, and even fewer recalled being given the option of banking sperm (51%). A pilot study by the same group18 revealed that only 57% of reproductive-aged men and women who survived cancer received information from their health From the *Program in Reproductive and Adult Endocrinology, NICHD, NIH, Bethesda, Maryland; and †Department of Obstetrics and Gynecology, Georgetown University Hospital, Washington, DC. Reprint requests: Hyacinth Browne, MD, 10 Center Drive, CRC 1-E-3140, Bethesda, MD 20892. E-mail: brownehy@mail.nih.gov. Copyright

Lipid Cell Tumors in Two Women With von Hippel-Lindau Syndrome

BACKGROUND: Lipid-cell tumors are rare, functioning ovarian neoplasms. They have not been reported in women with von Hippel-Lindau syndrome, an autosomal-dominant tumor-suppressor gene mutation that is associated with renal cell carcinoma, and other vascular tumors. CASES: Two women with von Hippel-Lindau syndrome and kidney tumors were evaluated for secondary amenorrhea, hirsutism, and complex adnexal masses seen on computed tomography. The first patient had known renal cancer and bilateral adnexal masses, one with central necrosis. Because metastatic renal cell cancer could not be excluded on frozen section, bilateral salpingo-oophorectomy was performed. The second patient underwent right salpingo-oophorectomy after human chorionic gonadotropin testing confirmed that the ovarian tumor produced testosterone. Final pathology in both cases revealed testosterone-secreting lipid cell tumors. CONCLUSION: Lipid cell ovarian tumors should be considered in women with von Hippel-Lindau presenting with adnexal mass, amenorrhea, and hirsuitism.

Ovarian response in women undergoing ovarian stimulation after myomectomy

OBJECTIVE To examine ovarian response in infertile women undergoing ovarian stimulation after abdominal myomectomy. DESIGN Case report. SETTING Academic medical research center. PATIENT(S) Four infertile women with known fibroids who had a failed assisted reproductive technology (ART) cycle followed by an abdominal myomectomy. INTERVENTION(S) Infertile women with known fibroids who had a failed ART cycle, from January 2000 to December 2006, followed by an abdominal myomectomy and a subsequent ART cycle. MAIN OUTCOME MEASURE(S) Ovarian function before (baseline) and after myomectomy was assessed by age, day 3 and day 10 FSH levels, days of stimulation, total gonadotropins used, peak E(2) level, the number of oocytes retrieved and embryos obtained, the number of high-grade embryos, and pregnancy outcome. RESULT(S) The mean age was 35 and 36 years before and after myomectomy, respectively. All subjects had uterine factor infertility. Two of these women also had tubal factor infertility, and one had endometriosis and male factor infertility. There was no difference in ovarian response before and after myomectomy. CONCLUSION(S) As expected, abdominal myomectomy did not adversely affect ovarian response in infertile women undergoing ovarian stimulation after a failed ART cycle. Larger randomized prospective studies are needed to accurately assess whether myomectomy has a negative impact on ovarian response.