Purpose: Treatment with cyclophosphamide (CYC) confers up to a 40% risk of ovarian failure in women of reproductive age. The use of GnRH agonists (GnRHa) to preserve ovarian function has been investigated in several small studies. We performed a systematic review of studies examining whether a GnRHa administered during chemotherapy is protective of ovarian function and fertility. Methods: We searched the English-language literature (1966( -April 2007 using MEDLINE and meeting abstracts and included studies that reported an association between GnRHa and ovarian preservation in women receiving chemotherapy. Studies without a control group were excluded. Ovarian preservation was defined as the resumption of menstrual cycles and a premenopausal follicle-stimulating hormone (FSH) after chemotherapy. Fertility was determined by a woman's ability to become pregnant. We estimated the summary relative risk (RR) and associated 95% confidence intervals (95% CI) using a random-effects model. Results: Nine studies included 366 women. Three studies included women with autoimmune disease receiving CYC; six included women with hematologic malignancy receiving combination chemotherapy. In total, 178 women were treated with GnRHa during chemotherapy, 93% of whom maintained ovarian function. Of the 188 women not treated with GnRHa, 48% maintained ovarian function. The use of a GnRHa during chemotherapy was associated with a 68% increase in the rate of preserved ovarian function compared with women not receiving a GnRHa (summary RR ¼ 1.68, 95% CI 1.34-2.1). Among the GnRHa-treated women, 22% achieved pregnancy following treatment compared with 14% of women without GnRHa therapy (summary RR ¼ 1.65, CI 1.03-2.6). Conclusions: Based on the available studies, GnRHa appear to improve ovarian function and the ability to achieve pregnancy following chemotherapy. Several randomized trials are underway to define the role and mechanism of GnRHa in ovarian function preservation. In the meantime, premenopausal women facing chemotherapy should be counseled about ovarian preservation options, including the use of GnRHa therapy.

In this cohort of young women with rheumatologic disease, more women with prior CYC than without had amenorrhea, nulliparity, and infertility. GnRH-a co-therapy may prevent these adverse effects of CYC.

Objective Standard treatment for severe granulomatosis with polyangiitis (GPA, previously Wegener’s granulomatosis) is daily oral cyclophosphamide (CYC), a cytotoxic agent associated with ovarian failure. In this study we assessed the rate of diminished ovarian reserve in women with GPA who received CYC versus methotrexate (MTX). Methods Patients in the Wegener’s Granulomatosis Etanercept Trial received either daily CYC or weekly MTX and were randomized to etanercept or placebo. For all women under 50, plasma samples taken at baseline or early in the study were evaluated against samples taken later in the study to compare levels of anti-Müllerian hormone (AMH) and follicle stimulating hormone (FSH), endocrine markers of remaining egg supply. Diminished ovarian reserve was defined as AMH<1.0ng/ml. Results Of 42 women in this analysis (mean age 35), 24 had CYC exposure prior to enrollment and 28 received the drug during the study. At study entry, women with prior CYC exposure had significantly lower AMH, higher FSH, and a higher rate of early menstruation cessation. For women with normal baseline ovarian function, 6/8 who received CYC during the trial developed diminished ovarian reserve, compared to 0/4 who did not receive CYC (p<0.05). Changes in AMH correlated inversely with cumulative CYC dose (p=0.01), with a 0.74ng/ml decline in AMH for each 10g of CYC. Conclusion Daily oral CYC, even when administered for less than 6 months, causes diminished ovarian reserve, as indicated by low AMH levels. These data highlight the need for alternative treatments for GPA in women of childbearing age.

We report on a child with dextrocardia, atrial septal defect (ASD), severe developmental delay, hypotonia, 13 pairs of ribs, left preauricular choristoma, hirsutism, and craniofacial abnormalities. Prenatal cytogenetic evaluation showed karyotype 46,XY,?dup(8p)ish del(8)pter. Postnatal array CGH demonstrated a 6.8 Mb terminal deletion at 8p23.3–p23, an interstitial 31.1 Mb duplication within 8p23.1–p11, and a terminal duplication of 0.24 Mb at 22q13.33, refining the karyotype to 46,XY,der(8)dup(8)(p23.1p11.1)t(8;22)(p23.1;q13.1).ish der(8)dup(8)(p23.1p11.1)t(8;22)(p23.1;q13.1) (D8S504‐,MS607 + ,ARSA + ,D8Z1 + , RP115713 + +). Previous reports of distal 8p deletion, 8p duplication, and distal 22q duplication have shown similar manifestations, including congenital heart disease, intellectual impairment, and multiple minor anomalies. We correlate the patient's clinical findings with these particular areas of copy number. This case study supports the use of aCGH to identify subtle chromosomal rearrangement in infants with cardiac malformation as their most significant or only apparent birth defect. Additionally, it illustrates why aCGH is essential in the description of chromosome rearrangements, even those seemingly visible via routine karyotype. This method shows that there is often greater complexity submicroscopically, essential to an adequate understanding of a patient's genotype and phenotype. © 2012 Wiley Periodicals, Inc.