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Breast cancer is the most common cancer in reproductive age women, and treatment can affect fertility; however, there is often concern regarding the safety of increased estradiol (E2) levels and potential delays in treatment with ovarian stimulation for fertility preservation (FP). The aim of this study was to compare recurrence and survival in breast cancer patients who pursued FP without concurrent letrozole to those who did not (non-FP). We reviewed charts of women with breast cancer who contacted the FP patient navigator (PN) at Northwestern University from 01/2005–01/2018. Oncology and fertility outcome data were collected. Data were analyzed by Chi-square test or regression, as appropriate. Kaplan–Meier curves were used to examine breast cancer recurrence and survival. Statistical analyses were performed with SPSS IBM Statistics 26.0 for Windows. 332 patients were included, of which 157 (47.3%) underwent FP. Median days to treatment after consulting the PN was 35 in the FP group and 21 in non-FP (p

Breast cancer is the most common cancer in reproductive age women, and treatment can affect fertility; however, there is often concern regarding the safety of increased estradiol (EWe reviewed charts of women with breast cancer who contacted the FP patient navigator (PN) at Northwestern University from 01/2005-01/2018. Oncology and fertility outcome data were collected. Data were analyzed by Chi-square test or regression, as appropriate. Kaplan-Meier curves were used to examine breast cancer recurrence and survival. Statistical analyses were performed with SPSS IBM Statistics 26.0 for Windows.332 patients were included, of which 157 (47.3%) underwent FP. Median days to treatment after consulting the PN was 35 in the FP group and 21 in non-FP (p 0.05). Cancer recurrence was noted in 7 (4.7%) FP patients and 13 (7.9%) non-FP patients (NS), and mortality in 5 (3.2%) FP patients and 7 (4.2%) non-FP patients (NS). Within the FP group, no significant differences were found in recurrence or mortality based on ER status, age, BMI, peak EFP is safe and effective in breast cancer patients, regardless of receptor status; E

Objective To compare long-term outcomes of cancer patients who pursued fertility preservation (FP) with those who did not and compare random-start (RS) and menstrual cycle–specific (CS) protocols for FP. Design Retrospective cohort. Setting Single urban academic institution. Patient(s) Oncology patients who contacted the FP patient navigator, 2005–2015. Intervention(s) None. Main Outcome Measure(s) Time to cancer treatment, disease-free survival, and reproductive outcomes in FP versus no-FP patients and cycle outcomes for RS versus CS protocols. Data were analyzed by χ 2 and logistic regression. Result(s) Of 497 patients who met the inclusion criteria, 41% elected FP. The median number of days to cancer treatment was 33 and 19 days in the FP and no-FP groups, respectively. There was no difference in cancer recurrence or mortality. There were no differences in stimulation parameters, outcomes, or days to next cancer treatment in RS versus CS protocols. Twenty-one patients returned to use cryopreserved specimens, resulting in 16 live births. Eight of 21 returning patients used a gestational carrier. Thirteen FP (6.4%) and 16 no-FP (5.5%) patients experienced a spontaneous pregnancy. Conclusion(s) FP is both safe and efficacious for eligible cancer patients. Only 10% of patients returned to use cryopreserved specimens, and almost half used a gestational carrier, suggesting the need for further research into reproductive decision-making in cancer survivors.

Context : Cancer survival has improved significantly and maintaining fertility is both a major concern and an important factor for the quality of life in cancer patients. Aims : To explore differences in oocyte stimulation for fertility preservation (FP) patients based on cancer diagnosis. Settings and Deign : Between 2005 and 2011, 109 patients elected to pursue FP at a single institution. Materials and Method : In vitro fertilization (IVF) outcome variables between four cancer diagnostic groups (breast, gynecologic, lymphoma/leukemia and other) and age-matched male factor or tubal factor infertility IVF control group were compared. Statistical Analysis : ANOVA and Chi-square analyses were employed to compare variables between the groups that were normally distributed. Kruskal-Wallis with subsequent Mann-Whitney U-test were used for data that were not normally distributed. Results : Women with gynecologic malignancies were significantly older than the women in the other three groups, but tended to have a better ovarian response. Women with hematologic malignancies were most likely to have been exposed to chemotherapy and had the longest stimulations with a similar number of oocytes retrieved. The age-matched IVF controls had higher peak estradiol levels, number of oocytes obtained, and fertilization rates when compared to cancer patients with or without a history of prior chemotherapy. Conclusions : Factors including age, type of cancer and chemotherapy exposure, can influence response to ovarian stimulation. Discussing these findings with patients presenting for FP may aid in setting realistic treatment expectations.

Approximately 10%-15% of clinically recognized pregnancies end with a first trimester loss. Cytogenetic analysis of products of conception (POC) has revealed that a large proportion of these spontaneous miscarriages are a result of chromosomal abnormalities. However, relatively few studies have evaluated chromosomal abnormalities in pregnancies achieved using assisted reproductive technologies (ART). Here, we review the incidence and type of chromosomal abnormalities that occurred in our infertility patient population undergoing ART and provide a review of the literature pertaining to this subject.A retrospective chart review of all patients from our medical center who conceived using ART between January 2000 and January 2008, who experienced a subsequent early pregnancy loss, and whose POCs were successfully karyotyped were included. We also conducted a literature review in PubMed, searching for other articles on this subject.Two hundred fourteen patients conceived with ART, experienced an early loss, and subsequently underwent a dilation and curettage (DC) between 2000 and 2008. A total of 59 (27%) patients chose to have cytogenetic testing, and their POCs were successfully karyotyped. The overall rate of aneuploidy in this group was 83%. Our PubMed search revealed a total of 12 studies that were identified and evaluated and deemed appropriate for review.Consistent with most of the literature, we found a high rate of aneuploidy present in infertile patients conceiving using ART. Because an abnormal karyotype provides an explanation for an early loss, this and other studies seem to suggest that routinely carrying out this assessment in such patients may be of value.

Objective To evaluate the influence of "true" versus "sham" acupuncture on pregnancy rates (PRs) in women undergoing IVF. Design Randomized controlled trial, double-blinded with independent observer. Setting Academic infertility clinic. Patient(s) One hundred sixty patients Intervention(s) Subjects were randomly allocated to the true or sham group and underwent acupuncture 25 minutes before and after ET. Subjects completed a McGill Pain Questionnaire regarding their clinical symptoms during ET. Main Outcome Measure(s) Clinical PR and clinical symptoms during ET. Result(s) While the overall clinical PR was 51.25%, there was no significant difference between the arms of the study (true = 45.3% vs. sham=52.7%); 33.1% of the patients had ultrasound-documented singleton pregnancy, and 15% of patients had twin gestations, while one patient in the true arm had a triplet gestation. There were significant differences in the subjective, affective, and total pain experience between both arms. The subjects in the true arm described their acupuncture session as being more "tiring" and "fearful" and experienced more "achiness" compared with their sham counterparts. Conclusion(s) There was no statistically significant difference in the clinical or chemical PRs between both groups. Patients undergoing true acupuncture had differing sensory experiences compared with patients in the sham arm. There were no significant adverse effects observed during the study, suggesting that acupuncture is safe for women undergoing ET.

With the advent of evidence-based medicine, much of the complex testing that infertile couples used to undergo is no longer recommended as part of the routine evaluation. Examples of tests no longer implemented include the postcoital test, Rubin test of tubal patency, endometrial biopsy, sperm antibody testing, and the zona-free hamster test. The role of routine diagnostic laparoscopy and hysteroscopy is also reviewed.In 2010, the simplicity of the current evaluation of couples presenting with infertility is essential information for patients to know at the initial visit. Ideally, it can help alleviate anxiety and provide patients with a road-map during a visit that is often associated with stress and high emotions.ObstetriciansGynecologists, Family Physicians.After completion of this educational activity, the obstetrician/gynecologist should be better able to assess the current recommendations for evaluating infertile couples; examine the various ways to assess ovarian reserve, the uterine cavity, and fallopian patency; and appraise the controversy surrounding diagnostic surgery.

Objective To characterize the early experience of a clinical program designed to provide strategies for fertility preservation to female cancer patients about to undergo chemotherapy or radiation therapy. Design Retrospective chart review; case–control study. Setting Academic medical center. Patient(s) Sixty-five female cancer patients and 57 age-matched infertility patients. Intervention Enrollment in a program for fertility preservation. Main Outcome Measure(s) Choice of active participation, fertility preservation option selection, clinical outcomes of patients undergoing oocyte retrieval, attitudes regarding embryo disposition. Result(s) Of 65 patients referred to the program, 18 declined to undergo embryo, oocyte, or tissue cryopreservation. Six were found not to be eligible for medical reasons. Of the remaining 41 patients, 35 chose to cryopreserve embryos, four chose to cryopreserve oocytes, and two chose to undergo ovarian tissue freezing. Fewer oocytes were recovered from the embryo cryopreservation group when compared with an age-matched control group, but the mean number of zygotes generated was similar. Attitudes regarding embryo disposition were different between the two groups. No serious clinical sequelae resulted from participation. Conclusion(s) Fertility preservation techniques employing available technology may provide safe and practical options to female cancer patients facing chemotherapy or radiation therapy. A significant number of otherwise appropriate participants decline active management. Cancer patients display different attitudes regarding embryo disposition when compared with infertility patients without cancer.

The mechanisms and physiology of reproductive function have fascinated scientists throughout time. Recent cellular and molecular level structural studies have provided unprecedented insights into reproductive systems and signaling networks. This ‘cutting edge’ editorial provides a recent example in each of these areas, namely, the anatomical integrity of the follicle, the molecular structure of activin with its binding partners and the molecular regulation of inhibin. These three examples of structure informing function help explain reproductive health and may provide solutions to reproductive disease.

Objective To examine the association between first-trimester bleeding and live-birth rates in twin pregnancies conceived with in vitro fertilization (IVF). Design Retrospective cohort study. Setting Academic infertility practice. Patient(s) Women with two gestational sacs on first-trimester ultrasound after transfer of fresh embryos derived from autologous oocytes between January 1, 1999, and December 31, 2010. Intervention(s) None. Main Outcome Measure(s) Live-birth rate. Result(s) Sixty-five women reported vaginal bleeding, and 288 did not. The baseline characteristics were similar between the two groups, except for an increased prevalence of subchorionic hematoma in women with first-trimester vaginal bleeding (26.2% vs. 1.7%). Live-birth rates were similar between women with bleeding and those with no bleeding (87.7% vs. 91.7%, adjusted odds ratio [OR] 0.73; 95% confidence interval [CI], 0.31–1.73). Two hundred eighty-eight women gave birth to live twins. Among the women who delivered twins, those with first-trimester bleeding had an increased risk of low birth weight of at least one twin (75.0% vs. 59.7%). The association between bleeding and low birth weight persisted after controlling for possible confounders with logistic regression (adjusted OR 2.33, 95% CI, 1.14–4.74). Conclusion(s) Live-birth rates are high in IVF twin gestations, regardless of the presence of first-trimester bleeding. Among women giving birth to IVF twins, however, first-trimester bleeding is associated with increased odds of low birth weight.

Despite evidence supporting the involvement of the IGF system in the development of breast and other cancers, the major determinants of interindividual variability in circulatory IGF-I levels are not well understood. Previous research has pointed to important genetic influences as well as dietary effects through marked calorie or protein restriction. We conducted a randomized trial to determine the effects of 2 dietary patterns on serum IGF-1, IGFBP1 and IGFBP3 in free-living premenopausal women: phase 1, an isocaloric low-fat, high-fiber (LFHF) vs. usual diet, and phase 2, a soy supplement either with or without isoflavones (soy+IF vs. soy-IF). Participants completed 12 menstrual cycles on phase 1 and then were randomly assigned to a soy supplement for 3 cycles while maintaining the phase 1 diet. Before and after each phase, 154 women provided serum. We found no difference in the change in IGF-I, BP1 or BP3 in the LFHF group compared to the usual diet group. In phase 2, there were no differences in any IGF protein between the soy+IF and the soy-IF groups or any evidence of interaction between isoflavone exposure and the background diet. However, there was a small but statistically significant decrease (2.3%) in BP3 and an increase in the IGF-I:BP3 molar ratio among all 153 subjects following either soy supplement. These changes were correlated with changes in intake of calcium, total vegetable protein and soy. The results are compatible with previous data suggesting that increases in dietary calcium, protein and soy, in particular, could increase circulating levels of bioavailable IGF-I.

Objective To prospectively assess anxiety, depression, coping, and appraisal in female fertility preservation (FP) patients compared with infertile patients. Design Prospective pre- and post-treatment survey. Setting Academic medical center. Patient(s) Forty-seven women with cancer (FP patients) and 91 age-matched infertile patients. Intervention(s) None. Main Outcome Measure(s) Depression, anxiety, coping, infertility-related stress, appraisal of treatment, and medical outcomes. Result(s) FP patients reported more symptoms of anxiety and depression than infertile patients, but infertile patients' symptoms worsened over time; 44% of FP and 14% of infertile patients' scores exceeded the clinical cutoff for depression before treatment. The interval between surveys and medical treatment data did not predict changes in mood symptoms. Coping strategies and infertility-related stress did not differ between groups, and avoidant coping predicted higher depression and anxiety scores. Conclusion(s) FP patients reported more anxiety and depression than infertile patients at enrollment in treatment, with more than one-third of FP patients reporting clinically significant depressive symptoms. However, infertile patients' anxiety and depressive symptoms increased across treatment. This increase was not related to time between registration for IVF and oocyte retrieval or the medical aspects of treatment. FP and infertile patients should be provided psychologic consultation before treatment to identify mood and anxiety symptoms and to refer patients for counseling as needed to prevent worsening of symptoms.

Objective: To determine whether second-trimester serum concentrations of insulin, insulin-like growth factor-I (IGF-I), and insulin-like growth factor binding protein-1 (IGFBP-1) were altered in women before they developed clinical signs of preeclampsia. Methods: A nested case-control study used serum obtained during second-trimester pregnancies from 12 women who developed preeclampsia matched with 24 controls who remained normotensive. Nine preeclamptic subjects and 18 controls were necessary to have 80% power to discern a 20% difference between groups with regard to the analytes under consideration. Results: There were no significant differences between cases and controls with respect to many demographic factors. Women who developed preeclampsia had insulin concentrations that were not significantly different from controls, but serum concentrations of IGF-I were significantly higher and IGFBP-1 were significantly lower than those of the controls. The IGF-I/IGFBP-1 ratio helped to identify those at risk for developing preeclampsia. Conclusions: Serum concentrations of IGF-I and IGFBP-1 were abnormal long before women manifested clinical evidence of preeclampsia in this study. These alterations might be related to abnormalities in trophoblastic invasion and prove useful as potential markers for the identification of women who are at high risk of developing preeclampsia.

Objective: To identify factors that predict failure of linear salpingostomy requiring salpingectomy for ectopic pregnancy. Methods: Using a retrospective cohort, we examined the various risk factors of women with ectopic pregnancies presenting for conservative laparoscopic management. Success or failure of laparoscopic linear salpingostomy was the primary end point. Results: One hundred fifty-seven women underwent laparoscopic linear salpingostomy for ectopic pregnancy, of whom 120 had successful procedures and 36 had unsuccessful operations because of bleeding and needed subsequent salpingectomy either by laparoscopy or laparotomy. The likelihood of success of laparoscopic linear salpingostomy was unrelated to gestational age, size of the ectopic pregnancy, surgical technique, or experience of the surgeon or resident. However, median (quartiles) serum beta hCG levels were significantly higher in patients who underwent failed salpingostomy (10,103 [3549–19,962] IU/L) compared with those who underwent successful salpingostomy (1692 [565–3971] IU/L, P < .01). Median blood loss (225 [181–562] mL versus 100 [50–200] mL, respectively, P < .01) and mean (± standard error of the mean [SEM]) operating times (111.1 ± 6.1 minutes versus 76.8 ± 2.3 minutes, P < .01) were significantly greater with failed salpingostomy followed by salpingectomy, compared with successful salpingostomy. Conclusion: Preoperative serum beta hCG level was the only significant determinant of failure of laparoscopic linear salpingostomy for ectopic pregnancy. Morbidity due to intraoperative blood loss and operating time was significantly increased as a result of attempting and failing to complete laparoscopic linear salpingostomy.

Anordiol (2 alpha,17 alpha-diethynyl-A-nor-5 alpha-androstane-2 beta,17 beta-diol) has been variously characterized as an estrogen and as an antiestrogen. To more completely understand the pharmacological properties of this contraceptive steroid, simultaneous responses were studied in uterine, vaginal, and hepatic tissues. Rats received 4 daily sc injections with either anordiol, clomiphene citrate (CC), or the vehicle alone (C+) starting on the first day of pseudopregnancy. Uteri were traumatized on day 4 of pseudopregnancy, and rats were sacrificed 5 days later. A pseudopregnant group without uterine trauma served as a negative control (C-). Mean uterine weights per animal and cytosolic estrogen (EcR) and progesterone (PcR) receptor activities per g of DNA were all 5- to 7-fold greater in the C+ group than in the other groups (all p < 0.05). However, anordiol and CC suppressed uterine weight without suppressing the stromal proliferative response; the DNA content of the uteri of anordiol- and CC-treated rats was similar to that of C+ rats. Vaginal tissue exhibited estrogenic responses to anordiol and CC with an increase in epithelial stratification compared to the C+ and C- groups even though no difference in levels of EcR/g of DNA were expressed 5 days after the last antiestrogen dose. Binding affinities and serum E2 and progesterone (P) concentrations were not statistically different among the groups. In conclusion, anordiol produced responses in the uterus and vagina of the pseudopregnant rat which were indistinguishable from those of CC, and, therefore, we conclude that anordiol acts on these tissues as an antiestrogen.

Consideration of existing data regarding clinical and biochemical risk factors for the development of breast cancer leads to the hypothesis that enhanced insulin-like growth factor I (IGF-I) activity plays a significant role in the development of this disease. Abnormal IGF-I activity may be related to events occurring prenatally, during puberty, or during adult life. Insulin resistance, a common feature in populations characterized by high caloric intake, may result in the amplification of IGF-I action at the tissue level by altering serum concentrations of IGF-I binding proteins. Several approaches toward testing the hypothesis are proposed, and potential opportunities for clinical application are described.

This study was designed to assess the impact of selected medical interventions during labor upon cesarean section rates by comparing the maternal and neonatal outcomes of obstetrician- and nurse-midwife-managed low-risk private patients. All patients who delivered at Prentice Women's Hospital in Chicago, Illinois, from January 1, 1987 through December 31, 1990 were evaluated for low-risk criteria to be included in the study. During that time, the nurse-midwives delivered 573 patients and the obstetricians delivered 12,077 patients. Patients with fetal and maternal complications known to increase the cesarean section rate were eliminated from both groups. Eight percent of the nurse-midwife patients and 32% of the physician patients were eliminated, leaving 529 nurse-midwife patients and 8,266 physician patients. These patients were compared for race, parity, age, and birth weight. Information was collected from a perinatal data base and hospital computerized statistics. The rates of cesarean section, administration of oxytocin, analgesia, anesthesia, and infant outcome data were compared by chi-square analysis. Multiple logistic regression analysis was used to assess factors that predicted cesarean section. Nurse-midwife-managed patients had a significantly lower rate of cesarean section (8.5% versus 12.9%; P < .005) and operative vaginal delivery (5.3% versus 17%, P = .0001) than the physician-managed patients. Epidural anesthesia and oxytocin for induction and augmentation were used significantly more frequently in the physician-managed patients. Both interventions were associated with an increased rate of cesarean section. Fetal outcomes in the two groups were not statistically different. Women cared for by nurse-midwives had a lower cesarean section rate, fewer interventions, and equally good maternal and infant outcomes when compared with those cared for by physicians.

Maternal plasma IGF-I and hPL concentrations were examined in 10 singleton pregnancies and in 11 twin gestations near term. hPL concentrations were higher in the twin pregnancies (14.4 ± 2.4 μg/1 vs 6.9 ± 0.9 μg/1, P < 0.02). In contrast, plasma IGF-I concentrations were similar in the singleton and twin pregnancies (533 ± 45 μg/1 vs 572 ± 60 μg/1, respectively). IGF-I concentrations failed to correlate with hPL concentrations in either group separately or when all subjects were considered together. These data do not support the hypothesis that maternal IGF-I secretion is an hPL-dependent process.

Objective To study the impact of chronic infusions of cortisol phosphate on ovarian function in the cynomolgus monkey. Design Cortisol phosphate at doses of 5 or 15 mg/d or saline were infused for periods of up to 8 weeks using subcutaneously implanted osmotic pumps. Setting Animals were maintained in the Center for Experimental Animal Resources, Northwestern University. Main Outcome Measures Serum total and unbound cortisol concentrations, serum total and unbound progesterone (P) concentrations, urinary P metabolites. Results Mean increases in serum cortisol of 56% and 77% above control levels were achieved. Mean serum P concentrations were not decreased with low-dose cortisol phosphate infusion during the 12 days preceding menses, but mean serum P levels were decreased by 69% to 2.3 ng/mL during high-dose cortisol phosphate infusion. No corresponding decrease in excretion of conjugated immunoreactive P metabolites was found in daily urine samples during cortisol phosphate infusion, suggesting that production rates of P were unaltered by the cortisol phosphate treatment. Unbound serum cortisol increased by a mean of 162% above control levels during high-dose cortisol phosphate infusion, but no increase occurred in the percentage of unbound serum P. Conclusions We conclude that elevation of serum cortisol in the range observed in chronically stressed individuals may severely decrease the available P to target organs by displacement of P from plasma proteins but does not inhibit ovarian steroidogenesis or ovulation.

In vitro fertilization (IVF) and storage of the resulting embryos is currently a proven method of fertility preservation for women who face an immediate threat to their future fertility. This method, however, is suitable for a fraction of patients and depends on a number of factors that may include her diagnosis, age, partner status, willingness to accept donor sperm, desire to freeze embryos, and ability to pay for these services. As fertility preservation techniques evolve, it is critical that physicians continue to evaluate practice guidelines in order to offer a wider menu of fertility preservation options tailored to each patient’s specific clinical scenario, to the risk-benefit ratio and takes into consideration the patient’s values. Practice guidelines and consensus statements for fertility preservation for oncology patients reflect the current evidence based and ethical practices in the related disciplines of oncology and reproductive endocrinology. Both the American Society of Clinical Oncology (ASCO) and the American Society of Reproductive Medicine (ASRM) recently published guidelines to describe the circumstances under which fertility preservation should be discussed and to describe patients for which experimental methods, such as ovarian cryopreservation, may be suitable [1–3]. Taken together, these documents are comprehensive in their description of: 1. The need for discussion with patients about impaired fertility resulting from cancer treatment

Background: Cryopreservation of oocytes or fertilized embryos prior to initiation of chemotherapy offers women with cancer an opportunity for future pregnancy if fertility is compromised by treatment. To investigate the actual delay in starting chemotherapy associated with fertility preservation protocols in young women with lymphoma, we performed a retrospective chart review of the Northwestern Medicine (NM) institutional experience. Methods: Subjects were identified from a log of women who contacted the fertility preservation patient care navigator (FPPCN) from May 2007 through December 2014. NM practitioners are required to address fertility in all newly diagnosed cancer patients, through the use of automated prompts. Patients were included in the analysis if they had newly diagnosed or relapsed/refractory lymphoma and were treated at NM, whether or not they attempted fertility preservation. The primary endpoint was time to treatment (TTT) initiation. In newly diagnosed patients, TTT was defined as time from NM hematology/oncology consult until the initiation of chemotherapy. In patients with relapsed disease, TTT was measured from time of biopsy at NM or time of consult if biopsy was performed at an outside institution. We used a one-tailed T test to compare independent means with a significance level of 0.05. Results: 128 lymphoma patients contacted the FPPCN between 5/2007- 12/2014 and data on 28 of 36 women who proceeded with fertility preservation (FP) is available for analysis. 50 of 93 lymphoma patients who contacted the FPPCN but did not undergo ovarian stimulation served as a comparison group. The average length of follow up was 152 weeks (range: 14-388 weeks). Reasons patients were excluded from the analysis included lack of chemotherapy treatment records and no treatment received at NM. Among patients undergoing FP, 21 presented with a new diagnosis and 7 with relapsed/refractory disease. The average age was 26 years (range: 20-31). All had ECOG PS of 0/1. Histologies were: 17 HL, 8 DLBCL, and 3 other subtypes. 25 patients had stage I/II and 3 had stage III/IV disease. 4 HL patients had early favorable disease, 12 early unfavorable, and one had advanced disease. Among 50 control patients, 37 presented with a new diagnosis and 13 with relapsed or refractory disease. The average age was 29 years (range 19-45). Histologies included 29 HL, 10 with DLBCL, 11 with other histologies. 31 patients were stage I/II and 15 were stage III/IV 15. 3 HL patients had early favorable disease, 19 had early unfavorable, and 6 had advanced disease with IPS scores ranging from 0-4. Among 28 FP patients, median TTT was 28 days (range: 8-76) versus 15.5 days (range: 0-74) in controls (p-value Discussion: Fertility preservation delayed treatment by a median of 13 days compared to controls. There was no difference in treatment delay among patients using the random start versus cycle specific protocols. However, all patients on the random start protocol were off oral contraceptives (OCP's) whereas almost all cycle specific patients were on OCP's, thus allowing them optimal timing of their cycle and reduced time to retrieval. The relapse free survival rate was lower among FP patients compared to controls (78% versus 94% respectively), however this did not meet statistical significance. Patients undergoing FP represent a selected group of patients with high risk disease, and baseline characteristics independent of FP may place them at increased risk of relapse. Whether or not the nearly two week delay required for fertility preservation results in adverse patient outcomes will require further investigation utilizing matched controls. Disclosures Gordon: Dr Leo I. Gordon: Patents & Royalties: Patent for gold nanoparticles pending; Northwestern University: Employment.

Objective To search for differentially expressed genes in cumulus cells from two groups of oocytes with different developmental outcome in vitro. Design Analyses of gene expression in human cumulus cells from oocytes that failed to fertilize in vitro (group A) and those that developed into normal-appearing embryos on day 3 (group B). Setting University-based facilities for clinical service and research. Patient(s) Women undergoing IVF treatment for infertility. Intervention(s) Cumulus cells were collected from oocytes that were aspirated from ovarian follicles for IVF. The oocytes were cultured individually for IVF and embryo development. Total RNA was extracted from the cumulus cells for gene expression analyses. Main Outcome Measure(s) General gene expression profiles and relative abundance of pentraxin 3 (Ptx3) mRNA. Result(s) DNA microarray analysis identified 160 genes, including Ptx3, that were differentially expressed between cumulus cells in group A and group B. Quantitative analysis confirmed that the relative abundance of Ptx3 mRNA in cumulus cells was highly associated with oocyte development. Conclusion(s) This study demonstrated that changes in the expression levels of 160 genes, including particularly Ptx3, in human cumulus cells may be indicative of the quality of their enclosed oocyte.

Objective To investigate the impact of delaying the transfer of in vitro fertilized embryos to day 5 on embryo development by comparing serum β-hCG levels in pregnancies established after day 3 embryo transfers and those after day 5 blastocyst transfers at equivalent time intervals after fertilization. Design A retrospective analysis. Setting Assisted reproductive technology center in an academic research environment. Patient(s) Women who had an embryo transfer procedure performed after in vitro fertilization (IVF) at Northwestern University's IVF Program between January 1999 and December 2001 were included in this study. Intervention(s) Embryo transfer was performed either on day 3 or day 5 after oocyte retrieval for IVF (day 0), depending on the availability of good-quality embryos on day 3. Main outcome measure(s) Serum β-hCG concentrations determined 13 and 15 days after fertilization in pregnancies established by transferring cleavage-stage embryos on day 3 or blastocysts on day 5. Result(s) In singleton pregnancies, serum β-hCG concentrations were 75 ± 54 (mean ± SD, n=203) or 62 ± 41 (n = 109) IU/mL after day 3 or day 5 transfers, respectively. In twin pregnancies, the β-hCG concentrations were 162 ± 105 (n = 52) or 109 ± 55 (n = 49) after day 3 or day 5 transfers, respectively. The percentage increases in β-hCG concentrations between the first and second measurements were similar in the two groups (day 3: 144 ± 109, day 5: 142 ± 63, not statistically significant). Conclusion(s) Initial β-hCG concentrations in pregnancies resulting from day 5 transfers were lower than those from day 3 transfers when assessed at equivalent intervals from fertilization. This suggests that embryo development or implantation may be impaired by the additional 2 days in culture.

To examine possible relationships between endometrial thickness and treatment outcome after IVF and embryo transfer, and to explore the role of potential confounding factors that may influence such relationships.Retrospective study.A university-affiliated clinical IVF center.Patients undergoing IVF-embryo transfer with their own oocytes.None.Endometrial thickness was determined on the day of hCG administration, 2 days before oocyte retrieval. Clinical pregnancy was confirmed by ultrasound observation of fetal heart activity.The study analyzed 897 IVF-embryo transfer cycles. Treatment outcome (clinical pregnancy) after IVF-embryo transfer was positively associated with increased endometrial thickness and peak E(2) concentrations in serum, and negatively associated with advanced age. Endometrial thickness was dependent on peak E(2) concentrations in serum, but was independent of patient age or duration of ovarian stimulation. Thin endometrium reduced PRs in relatively young patients (38 years old), in patients who required more than 10 days of gonadotropin stimulation, or in patients whose embryo transfers consisted of poor quality embryos.Increased endometrial thickness was associated with improved treatment outcome, but this association was dependent on patient age, duration of ovarian stimulation, and embryo quality.

Objective To examine the relationships between peak serum estradiol (E 2 ) levels and treatment outcome in in vitro fertilization (IVF) cycles after embryo transfer (ET) on day 3 or day 5. Design Retrospective analysis of 697 IVF-ET cycles between January 1999 and December 2001. Setting A university-affiliated assisted reproduction program. Patient(s) Infertile patients undergoing IVF-ET cycles. Intervention(s) Peak E 2 concentration in serum was determined on the day of human chorionic gonadotropin (hCG) administration. The IVF-generated embryos were cultured for 2 days until transfer on day 3. If more than four 8-cell embryos were present on day 3, embryo culture was continued until day 5 for blastocyst transfer. Main outcome measure(s) Clinical pregnancy rates. Result(s) High peak E 2 levels did not adversely affect treatment outcome. After the cycles were divided according to the day of ET, high peak E 2 levels were associated with improved pregnancy rates after ET on day 5 but not on day 3. Conclusion(s) Increasing peak E 2 levels in IVF cycles are associated with improved pregnancy rates after ET on day 5.

GnRH agonist administered early in the menstrual cycle (flare) causes an endogenous discharge of FSH and LH. Flare has been used in conjunction with gonadotropin ovarian stimulation for IVF 'poor responders'. There is an ongoing controversy regarding whether flare protocols improve pregnancy rates in 'poor responders'. The current study was designed to compare a GnRHa flare protocol with long suppression GnRHa IVF in 'poor responders'.Seventy-three newly diagnosed poor responders who failed long GnRHa suppression IVF attempts were compared retrospectively with 128 age-matched IVF patients previously known poor ovarian responders treated with a long GnRHa suppression protocol. 'Poor responders' consisted of patients with peak E(2) less than 1000 pg/ml and/or less than five mature follicles with diameter15 mm on the day of hCG administration. Student's t-test was used to analyze the data and the chi-squared test was used to compare fertilization and pregnancy rates.The flare protocol produced higher peak E(2) levels (1647+/-747 vs. 720+/-258 mIU/ml, P0.05) and a larger number of mature follicles (5.8+/-2.2 vs. 4.0+/-1.0 P0.05) in the study vs. the control group. A 30% pregnancy rate was achieved during this second IVF attempt using GnRHa flare protocol in the study group vs. 37 in the control group (P0.05, NS).A comparison between the flare protocol group and the age-matched control group of poor ovarian responders subject to down regulation protocol, revealed higher peak E(2) levels and more mature follicles, respectively. However, both groups yielded comparable pregnancy rates. The use of high dose gonadotropin treatment in our study groups seems to be the only explanation for their subsequent successful outcome. We concluded that GnRH agonist flare protocol does not result in better IVF outcome compared with long GnRH agonist suppression protocol in IVF poor responders.

The administration of GnRH-a for decreasing the size of uterine leiomyomata is tolerated by most of our patients with a minimum of side effects and difficulty. An unusual case of pseudo-Meigs' syndrome developed after a single dose of depot LA that resulted in an emergent operation in this young woman. The treatment of large leiomyomata uteri with GnRH-a warrants careful clinical surveillance.

A 38 year old woman was thought to have bilateral polycystic ovaries and an absence of pelvic or abdominal adhesions at diagnostic laparoscopy. Post-operative transvaginal ultrasound noted bilateral homogeneous hypo-echoic masses with low-level echoes consistent with endometriomas. Transvaginal aspiration was unsuccessful due to the viscosity of the cyst contents. At second laparoscopy severe adhesions with complete cul-de-sac obliteration were noted. This case raises concern about pelvic adhesions following transvaginal drainage of ovarian endometriomas.

1. Intravenous injection of [3H]progesterone in non-pregnant monkeys resulted in total disappearance of the labelled hormone from the circulation within 3 h. However, 0.5-1.75 h after disappearance the hormone reappeared, reaching 20% (median, 5%) of the initial maximal concentration. 2. Reappearance of labelled hormone was accompanied by similar fluctuations in the levels of labelled metabolites, [3H]20 alpha-dihydroprogesterone and [3H]17 alpha-hydroxyprogesterone, which reached 61% (median, 14%) and 120% (median, 13%), respectively, of the initial maximal concentrations. 3. Chromatography was used to separate labelled progesterone and its metabolites. Efficiency of the procedure was determined separately in each sample and for each steroid. All data were corrected for percentage recovery. 4. Analytical equations were devised, based on the theory of compartmental systems with continuously distributed time lags, to describe the unexpected kinetics of progesterone levels. The coefficients of determination ranged from 86 to 99% (median, 96%) which indicates that the equations enabled reliable prediction of hormone levels in blood within the time range studied. 5. The unexpected reappearance of labelled progesterone cannot be explained by hormone secretion but only by a delayed release from tissue stores, since progesterone does not undergo enterohepatic recirculation. Thus, a previously undescribed mechanism affecting circulating progesterone levels, and perhaps those of other hormones, exists.

Endometrial biopsies are of little value in the evaluation of infertile couples. Their usefulness in the evaluation of couples with repeated early pregnancy loss remains to be demonstrated.

In a retrospective chart review study women taking selective serotonin reuptake inhibitors antidepressants were compared with a matched comparison group to determine whether there were any differences in IVF outcome-related variables. There were no significant differences between the groups in peak E(2), number of oocytes retrieved, number of oocytes fertilized, percentage of 8-cell or blastocysts developed, day of transfer, or initial hCG values; however, 40% of women taking selective serotonin reuptake inhibitors had ongoing pregnancies compared to 51% of women not taking selective serotonin reuptake inhibitors.

Objective To assess the impact of ovarian hormone deprivation on serum concentrations of GH and insulin-like growth factor I (IGF-I) in women with polycystic ovarian syndrome (PCOS). Design Growth hormone and IGF-I levels were measured before, during, and at the end of a 6-month period of treatment with leuprolide acetate (LA) depot. Normal cycling and ovariectomized women served as controls. Setting The Clinical Research Center of Northwestern University Medical School. Patients Six women with PCOS, seven normal cycling women, and six ovariectomized women. Interventions The PCOS and normal cycling subjects were treated with six consecutive monthly injections of LA depot 3.75mg IM. Main Outcome Measures Circulating concentrations of GH and IGF-I. Results After 3months of treatment, GH levels decreased modestly in the PCOS group; however, these changes were not significant. No further decline was observed at 6months. Growth hormone levels were unaffected in the normal cycling group. Levels of IGF-I remained unchanged in both groups. Mean baseline levels of both GH and IGF-I in the ovariectomized group were lower than those of the normal cycling and PCOS groups at all time points, but not significantly so. Conclusions Medical castration fails to significantly alter serum GH and IGF-I levels in either normal cycling or women with PCOS. These data indicate that GH secretion is not modulated by hormones of ovarian origin in either group, at least over the period of time studied.

The purpose of the study was to assess the impact of subchronic hypercortisolemia on progesterone (P) metabolism and production and on peripheral LH levels in a nonhuman primate using a repeated measures experimental design. Osmotic pumps that released hydrocortisone phosphate (HP) at a dose of 15 mg/day were implanted sc in seven cynomolgus monkeys for two menstrual cycles. The pumps were filled with saline for the two control cycles, which either preceded (three animals) or followed (four animals) HP infusion. P metabolism, P production, and episodic secretion of LH were determined 8 +/- 1 days after the serum estradiol peak in the second control cycle and in the second cycle of HP infusion in each monkey, after iv bolus administration of 50 microCi [3H]P, followed by a 6-h blood sampling period. HP infusion elevated serum cortisol levels 1.6-fold. Serum P levels were decreased throughout the luteal phase by 58% (P < 0.01). The MCR of P and the volume of distribution at steady state of P were increased by 200% during HP infusion (both P < 0.005). The production rate of P was increased by HP treatment in five of seven monkeys. HP infusion increased the ratio of 20 alpha-[3H]dihydroprogesterone to [3H]P in serum from 0.5 to 1.0 (P < 0.05) while decreasing the fraction of [3H]P and its metabolites excreted in urine from 20% to 11% (P < 0.05). Serum LH levels, determined over a 5.25-h period in the luteal phase, were elevated by 200% during HP treatment (P < 0.05). Episodic secretion of LH during treatment was characterized by a 660% increase in the pulse amplitude (P < 0.05) and an apparent decrease in the pulse frequency. The results of this study provide evidence that moderate elevation of serum cortisol levels for two menstrual cycles in primates 1) increases the MCR of P, which may be the cause of the observed decrease in serum P levels; and 2) elevates serum LH levels by amplifying its pulse amplitude, which may result in a compensatory rise in the production rate of P.

Background: Artificial insemination is a commonly performed procedure for the treatment of various forms of infertility. Infectious complications have only rarely been noted as a complication of intrauterine insemination (IUI). Case: In this presentation, we report the first case of an ovarian abscess following IUI with the husband's semen. Despite treatment with triple antibiotics, an oophorectomy was required. Surgical as well as pathological evaluation confirmed the diagnosis of an ovarian abscess. Following surgery, the patient responded well to antibiotic therapy. Conclusion: Since pelvic infections are ascending processes, the violation of the natural cervical barrier with IUI can theoretically place the patient at increased risk for this complication. While few advocate routine cultures of semen samples, the clinician must be acutely alert to potential infectious morbidity following this procedure. Early diagnosis and intervention are necessary to minimize morbidity and optimize treatment.

To the Editor: The disposition of unused embryos is a pressing problem for in vitro fertilization programs.1,2 Although cryopreservation of embryos gives couples the chance to make additional attempts at pregnancy, unused frozen embryos create a storage problem and require couples to make difficult decisions regarding their disposition. Divorcing couples have had contentious disputes over embryos.3 In addition, interest in the use of these omnipotent cells for genetic research raises concern about unauthorized or inappropriate use. In vitro fertilization clinics offer these disposition options: continued cryopreservation, uterine transfer, donation to an infertile couple, donation to research, and disposal. In . . .

This study was performed to evaluate the effects of mechanical stimulation and sucrose treatment on the oocyte activation process. Fresh and aged human oocytes were exposed to sucrose and zonae were dissected with microneedles before fixation and quantitative analysis of cortical granules by transmission electron microscopy. Examination of the mean number of cortical granules/analyzed segment revealed no significant differences between control oocytes or oocytes treated with sucrose or sucrose treatment followed by zona dissection. A significant decline in the number of cortical granules/segment was observed for oocytes undergoing prolonged culture after dissection (P less than 0.05). Thus, zona dissection and sucrose exposure of freshly aspirated mature human oocytes do not result in classical oocyte activation.

To investigate the GH/insulin-like growth factor-I (IGF-I) axis in women with polycystic ovary syndrome (PCO), we measured serum concentrations of GH over a 14-h period (0900-2300 h) in 10 women with this disorder using an ambulatory exfusion pump. The same study was carried out in 9 age- and weight-matched normal cycling women who served as controls. Mean (+/- SE) serum GH concentrations over the 14-h period were markedly lower in the subjects with PCO (0.6 +/- 0.2 vs. 1.8 +/- 0.3 micrograms/L; P less than 0.005). Eight of 10 subjects with PCO had mean serum GH concentrations below 1.2 micrograms/L, while only 1 of 9 control subjects had corresponding values below this concentration. In contrast, mean circulating serum concentrations of IGF-I were indistinguishable in the 2 groups. We conclude from these data that PCO is characterized by decreased serum GH concentrations in the face of normal serum IGF-I concentrations. The mechanisms underlying this alteration in the GH/IGF-I axis and its role in the pathogenesis of PCO remain to be clarified.