Lucy J. Williams

Applicability of adult techniques for ovarian preservation to childhood cancer patients.

PurposeTo appraise the feasibility of current adult medical and surgical techniques for ovarian preservation in pre-pubertal and adolescent girls with cancer.MethodsLiterature search using PubMed and SCOPUS up to February 2012. In addition, the reference lists of selected studies and all identified systematic and narrative reviews were scanned for relevant references. Inclusion criteria were ovarian preservation and cancer. Exclusion criteria were non-English publications, letters, personal communications, and ovarian preservation for conditions other than cancer.ResultsData from the selected publications was interpreted and discussed in the relevant sections. Cryopreservation of ovarian tissue followed by autologous transplant represents the only surgical option available for pre-pubertal girls and adolescents who cannot delay the start of chemotherapy. Few studies report on pre-pubertal and adolescent girls undergoing ovarian preservation surgeries with good harvesting, and no follow-up has been conveyed, to date. Outcomes of ovarian function after ovarian suppression with GnRH-analogs in adults have been controversial and no reports are available for pre-pubertal girls.ConclusionsAutologous transplantation of cryopreserved ovarian cortex probably represents the best option for preservation of fertility and hormonal function in childhood cancer females; however, future research needs to address the safety of this technique, especially in patients with blood-borne cancers. Ovarian suppression with GnRH-analogs at the time of chemotherapy treatment has not proven to be superior to non-suppression for fertility preservation purposes in adults. Not enough evidence is presently available in childhood cancer patients.

Somatic and reproductive outcomes in mice treated with cyclophosphamide in pre-pubertal age.

Disruption in the normal timing of female puberty, such as in pre-pubertal cancer treatments, can cause abnormal somatic development. We sought to evaluate the impact of cyclophosphamide (CTX) on the somatic, uterine, and ovarian, development of pre-pubertal mice. Pre-pubertal (day 18 of life) C57BL/6J female mice were randomized to receive placebo (group 1A and 1B), 200 mg/kg CTX (group 2A), or 120 mg/kg CTX (group 2B). Mice were euthanized on day 56 (A groups) or 95 (B groups) of life. Body weight and length, uterine and ovarian weight and right femur length and weight were measured, and ovarian insufficiency was assessed. Data were analyzed using ANOVA and t-test. Body weight and length did not differ among groups at time of euthanasia. The femur was shorter and weighed less in mice treated with CTX than in controls. Uterine weight was lower in group 2B than 1B (46.1 mg, 95% CI: 42.9-49.4, vs. 62.2 mg, 95% CI: 58.5-65.8, respectively; p = 0.005) and was lower in mice that developed ovarian insufficiency than in mice that did not (p < 0.05). Ovarian weight was lower in mice treated with CTX, regardless of whether they developed ovarian insufficiency. Even with no observable effect on adult body length and weight, CTX treatment in pre-pubertal mice appears to negatively affect femur, uterine, and ovarian development. However, uterine development seems to be dependent on the hormonal status created by CTX more than on its direct effect.

Goserelin fosters bone elongation but does not prevent ovarian damage in cyclophosphamide-treated prepubertal mice

OBJECTIVE To evaluate whether administration of goserelin, a gonadotropin-releasing hormone (GnRH) agonist, could prevent acute or chronic ovarian insufficiency from cyclophosphamide (CTX) administration to prepubertal mice. DESIGN Animal study. SETTING University center. ANIMAL(S) C57BL/6J mouse strain. INTERVENTION(S) Goserelin administered on day 13 of life, CTX on day 18 of life, euthanasia on day 20 (prepubertal), 56 (pubertal), or 92 of life (mature), measurements of body weight, length, uterine weight, serum antimüllerian hormone and follicle-stimulating hormone, and histologic assessment of ovarian follicles and femur growth, and apoptotic rates by TUNEL. MAIN OUTCOME MEASURE(S) Assessment of prevention of ovarian insufficiency and defective bone elongation from CTX administration. RESULT(S) Prepubertal mice were randomly assigned to three groups: control (G1), CTX (G2), and goserelin + CTX (GG). A total of 63 mice were euthanized in the three groups. Body weight and length, and uterine weight did not differ among groups at any age. Ovarian size was not different in the three groups. There were fewer primordial and primary follicles/mm(2) in groups GG and G2 than in group G1 at all ages, but there was no difference between groups GG and G2. Corpora lutea/mm(2) were decreased in group GG versus G2. Femur length was statistically significantly greater in groups G1 and GG than group G2. CONCLUSION(S) Goserelin administered to prepubertal mice during CTX treatment fosters maintenance of bone elongation but does not protect the ovaries from follicular depletion.

Anti-Müllerian Hormone Serum Measurements Reflect Cycle Length and Ovarian Follicle Number in Women With Polycystic Ovary Syndrome [350]

INTRODUCTION: During folliculogenesis, anti-Müllerian hormone plays a key role in the selection of the dominant follicle. Levels of anti-Müllerian hormone are elevated in women with polycystic ovary syndrome (PCOS) and are correlated with the number of follicles. We explored the relationship of anti-Müllerian hormone with the PCOS-defining characteristics: clinical and biochemical hyperandrogenism, cycle length, ovarian volume, and antral follicular count. METHODS: Women diagnosed with PCOS by the Rotterdam criteria were included in the study. All underwent endocrine and ultrasound assessment in the early follicular phase. Anti-Müllerian hormone was included in a regression analysis model with the PCOS-defining characteristics (SPSS 21). RESULTS: A total of 153 women were included. Clinical hyperandrogenism (hirsutism, acne, or both) was present in 142 patients (92.8%). Anti-Müllerian hormone (5.4±5.2 ng/mL), cycle length (51.9±52.8 days), average follicle count (21.2±9.1), ovarian volume (11.2±6.0 mm3), testosterone (30.5±15.0 ng/dL), and FAI (3.0±2.6) were the evaluated variables (average±standard deviation). Of the PCOS-defining characteristics, anti-Müllerian hormone was predicted by cycle length (t=3.492, P=.001) and average follicle count (t=2.231, P=.03). Ovarian volume and clinical and biochemical hyperandrogenism were not found to be significant predictors. The results remained significant controlling for age and body mass index. CONCLUSION: Higher serum anti-Müllerian hormone levels were correlated with excessive follicular count and prolonged cycle length. These results underscore the inhibitory function of anti-Müllerian hormone on ovarian follicular development and could help explain the effect of an increased number of follicles on ovulation and fertility potential in women with PCOS.

Somatic and reproductive development in pre-pubertal mice treated with cyclophosphamide and subsequent estrogen replacement.

We tested the hypothesis that chemotherapy would prevent the expected pubertal development of uterus, ovaries, and long bones, and that estrogen replacement subsequent to treatment with chemotherapy would restore uterine and bone development to expected sizes. Pre-pubertal female C57BL/6J mice (n = 78) were assigned to receive placebo (controls), 200 mg/kg (group A), or 120 mg/kg (group B) of cyclophosphamide (CTX) on postnatal day 18. Mice were subsequently randomized to receive estradiol placebo or long-release estradiol pellet insertion on day 22 (early estradiol dose), day 45 (mid estradiol dose), or day 67 (late estradiol dose) of life. Body weight and length, uterine and ovarian weight, and right femur length and weight were measured. Mice treated with CTX had shorter and lighter femurs and lighter ovaries than controls (13.46 cm ± 1.51 cm vs. 15.00 cm ± 1.10 cm, 57.70 mg ± 9.71 mg vs. 65.30 mg ± 3.68 mg, and 5.16 mg ± 3.00 mg vs. 10.05 mg ± 2.31 mg, respectively; p < 0.05). Mice receiving estrogen replacement had a larger average body weight, BMI, and uterine weight than those that received placebo estrogen (19.56 g ± 1.82 g vs. 18.10 g ± 2.08 g, 26.53 g/cm2 ± 2.91 g/cm2 vs. 23.47 g/cm2 ± 3.06 g/cm2, 101.19 mg ± 41.69 mg vs. 50.00 mg ± 9.49 mg, respectively; p < 0.05). Cyclophosphamide treatment in pre-pubertal mice negatively affected femur and reproductive development. Estrogen treatment restored expected uterine development by maturity, regardless of the timing of administration. However, there was no similar recovery of femur length and bone mass was only partially recovered.

Fluid Deficit Calculation at Hysteroscopy: Could Calculation of Intraperitoneal Fluid Accumulation Add Insight to Safety Limits? [341]

INTRODUCTION: The literature and current guidelines are silent regarding the contribution of the fallopian tubes to the fluid deficit during hysteroscopy. Tubal opening pressure is reported as 75 mmHg; however, most hysteroscopic procedures require a higher intracavitary pressure to keep the cavity free of blood. The objective of this study is to show that the fluid deficit is not entirely the result of intravasation, but also attributable to passage of distention fluid into the peritoneal cavity through the fallopian tubes in women with patent tubes. METHODS: Operative reports and photographs of patients who underwent operative hysteroscopy and laparoscopy were reviewed. Suction canisters and automated fluid management systems were used to calculate the fluid deficit. Various suction devices were used during laparoscopy to remove fluid from the pelvis, which was measured. RESULTS: Fourteen patients were included in this study. All underwent hysteroscopy before laparoscopy. The average fluid deficit was 525.9 mL (95% confidence interval [CI] 482.1–569.7); posthysteroscopy peritoneal fluid at laparoscopy was 250 mL (95% CI 234.5–265.5); and the calculated fluid deficit resulting from intravasation was 286.6 mL (95% CI 253.0–320.3). One patient in the study had previously undergone bilateral tubal ligation and was found to have 0 mL of peritoneal fluid. CONCLUSION: During hysteroscopy, women with patent tubes have passage of distension fluid into the peritoneal cavity, which should be considered in the fluid deficit calculation. Because hospitals have different safety policies about discontinuation of hysteroscopic procedures based on the fluid deficit, our findings could aid in the implementation of more accurate and patient-centered safety protocols for hysteroscopic procedures.