Papers by Elizabeth Ginsburg
Fertility and Sterility, Sep 1, 2019
Reproductive Biology and Endocrinology, 2022
Background The utilization of oocyte cryopreservation (OC) has become popularized with increasing... more Background The utilization of oocyte cryopreservation (OC) has become popularized with increasing numbers of reproductive-aged patients desiring to maintain fertility for future family building. OC was initially used for fertility preservation in postmenarchal patients prior to gonadotoxic therapies; however, it is now available to patients to circumvent age-related infertility and other diagnoses associated with early loss of ovarian reserve. The primary aim of this paper is to provide a narrative review of the most recent and robust data on the utilization and outcomes of OC in both patient populations. Summary OC results in similar oocyte yield in patients facing gonadotoxic therapies and patients undergoing planned OC. Available data are insufficient to predict the live birth rates or the number of oocytes needed to result in live birth. However, oocyte yield and live birth rates are best among patients < 37.5 years old or with anti-mullerian hormone levels > 1.995 ng/dL, ...
The Journal of Clinical Endocrinology & Metabolism, 2017
The oncologist, Jul 1, 2017
Oncofertility is a unique, multidisciplinary field that serves to bridge the gap between availabl... more Oncofertility is a unique, multidisciplinary field that serves to bridge the gap between available fertility resources and the special reproductive needs of cancer patients. Oncofertility is a growing field due to the increasing number of survivors, development of new oncologic therapies, extension of duration of therapies, and development and refinement of reproductive therapies. While the technologies and demand for services expand, clinicians need to be appropriately prepared for dealing with various clinical scenarios that may require ethical deliberation. Three real cases are presented in which the patient wishes to pursue reproductive assistance, but her decision is met with hesitance or uncertainty by her care team. Discussion of these clinical scenarios highlights ethical implications of oncofertility practice and serves to highlight the need for the establishment of multidisciplinary care teams and guidelines to support both clinicians and patients. The growing field of onc...
Fertility and sterility, 2016
To determine whether public support for oocyte cryopreservation (OC) exists and if support varies... more To determine whether public support for oocyte cryopreservation (OC) exists and if support varies by demographic factors. Cross-sectional electronic survey. Not applicable. A nationally representative sample based on age, sex, and race of 1,064 people in the United States recruited by the company SurveyMonkey. Completion of an online questionnaire. Supporters of OC for various indications were compared with participants who were neutral or in opposition by means of log binomial regression to calculate risk ratios. Statistical models were adjusted for demographic characteristics, including sex, race, age, income, sexual orientation, education, marital status, state political party affiliation, and history of being a parent. OC for cancer patients was the indication most supported (89%), followed by delayed childbearing for career advancement (72%), current lack of a partner (63%), and insufficient funds for child rearing (58%). Despite considerable support for OC, only 37% agreed emp...
Fertility and sterility, Jan 13, 2016
This opinion addresses the ethics of providing fertility treatment to women at elevated risk from... more This opinion addresses the ethics of providing fertility treatment to women at elevated risk from fertility treatment or pregnancy. Providers ethically may treat women at elevated risk provided that they are carefully assessed; that specialists in their medical condition are consulted as appropriate; and that patients are fully informed about risks, benefits, and alternatives, including oocyte and embryo donation, use of a gestational surrogate, not undergoing fertility care, and adoption. Providers also may conclude that the risks are too high for them to ethically treat particular patients; such determinations must be made in a medically objective and unbiased manner and patients must be fully informed of the decision. Counseling of women who wish to initiate fertility treatment with underlying medical conditions that confer increased risk during treatment or pregnancy should incorporate the most current knowledge available, being cognizant of the woman's personal determinants...
Fertility Research and Practice, 2016
Background: In vitro fertilization (IVF) and pre-implantation genetic diagnosis (PGD) are becomin... more Background: In vitro fertilization (IVF) and pre-implantation genetic diagnosis (PGD) are becoming increasingly common techniques to select embryos that are unaffected by a known genetic disorder. Though IVF-PGD has high success rates, 7.5 % of blastocysts have inconclusive results after testing. A recent case involving a known BRCA-1 carrier was brought before our Assisted Reproductive Technology Ethics Committee in order to gain a better appreciation for the ethical implications surrounding the transfer of embryos with indeterminate testing. The case presentation: Thirty-nine year old G0 BRCA-1 carrier requiring IVF for male factor infertility. The couple elected for PGD to select against BRCA-1 gene carrier embryos. However, several embryos were returned with inconclusive results. The couple wished to proceed with the transfer of embryos with an unknown carrier status. The case was presented before our Assisted Reproductive Technology Ethics Committee. Conclusion: Many considerations were explored, including the physician's duty to protect patient autonomy, the physician's duty to act in the best interest of the future child, and the physician's duty towards society. Transferring both embryos with unknown carrier status and known-carrier status was debated. Ultimately, the transfer of inconclusive embryos was felt to be ethically permissible in most cases if patients had been adequately counseled. However, the re-biopsy of embryos with inconclusive testing results was encouraged. The transfer of known-carrier embryos was felt to be unethical for certain disease-states, depending on the severity of illness and timing of disease onset. We strongly encourage physicians to create an action plan in advance with their patients, prior to testing, in the event that embryos are returned with inconclusive PGD results. The committee's decision, though helpful in guiding practice, should not overshadow the individual physician-patient relationship, and the need for thorough counseling.
Fertility Research and Practice, 2015
Background: The causes of female infertility are multifactorial and necessitate comprehensive eva... more Background: The causes of female infertility are multifactorial and necessitate comprehensive evaluation including physical examination, hormonal testing, and imaging. Given the associated psychological and financial stress that imaging can cause, infertility patients benefit from a structured and streamlined evaluation. The goal of such a work up is to evaluate the uterus, endometrium, and fallopian tubes for anomalies or abnormalities potentially preventing normal conception. To date, the standard method for assessing these structures typically involves some combination of transvaginal sonography (TVS), hysterosalpingography (HSG), and hysteroscopy (HSC). The goal of this review is to compare the diagnostic accuracy of TVS, HSG, and HSC for diagnosing abnormalities in infertility patients to determine if all studies are necessary for pre-treatment evaluation. Results: We identified infertility patients prior to initiation of assisted reproductive technology who had baseline TVS, HSG, and HSC within 180 days of each other. From medical record review, we compared frequencies of each finding between modalities. Of the 1274 patients who received a baseline TVS over 2 years, 327 had TVS and HSG within 180 days and 55 patients had TVS, HSG and HSC. Of the 327, TVS detected fibroids more often than HSG (74 vs. 5, p < .0001), and adenomyosis more often than HSG (7 vs. 2, p = .02). HSG detected tubal obstruction more often than TVS (56 vs. 8, p = .002). Four (1.2 %) patients had endometrial polyps on both HSG and TVS. In the 55 patients with HSG, TVS, and HSC, HSC identified endometrial polyps more often than TVS (10 vs. 1, p = .0001) and HSG (10 vs. 2, p = .0007). TVS detected more fibroids than HSC (17 vs. 5, p < .0001). Tubal obstruction was identified more often by HSG than HSC (19 vs. 5, p < .0001). Conclusions: TVS is superior for evaluation of myometrial pathology. HSG is superior for evaluation of tubal pathologies. Endometrial pathologies are best identified with HSC.
Journal of assisted reproduction and genetics, Jan 15, 2015
Morphological evaluation is currently considered the single most important predictive measure for... more Morphological evaluation is currently considered the single most important predictive measure for assessing embryo quality. The aim of this study was to investigate whether cycles with at least one non-cleaved embryo (i.e., a 1-cell embryo on day 3) have different outcomes compared with cycles in which all embryos had cleaved by day 3. All autologous IVF/ICSI cycles with a fresh day 3 transfer and without using a gestational carrier performed at our center between 1/1/2010 and 12/31/2011 were analyzed retrospectively. Those cycles with at least one non-cleaved embryo on day 3 were compared with all other autologous cycles that had l00 % cleaved embryos performed during the study period. Eight hundred and forty two cycles were included. Of them, 144 cycles comprised the non-cleaved group, and 698 cycles comprised the cleaved group. Cycles in the non-cleaved group had more oocytes retrieved (15.4 ± 7.1 vs. 12.5 ± 7.1, p < 0.001), more zygotes obtained (10.0 ± 5.3 vs. 7.9 ± 5.2, p =...
Journal of Assisted Reproduction and Genetics, 2014
Purpose To evaluate the association between serum progesterone (P) levels on the day of embryo tr... more Purpose To evaluate the association between serum progesterone (P) levels on the day of embryo transfer (ET) and pregnancy rates in fresh donor IVF/ICSI cycles. Methods Fresh donor cycles with day 3 ET from 10/2007 to 8/2012 were included (n=229). Most cycles (93 %) were programmed with a gonadotropin releasing hormone (GnRH) agonist; oral, vaginal or transdermal estradiol was used for endometrial priming, and intramuscular P was used for luteal support (50-100 mg/day). Recipient P levels were measured at ET, and P dose was increased by 50-100 % if <20 ng/mL per clinic practice. The main outcome measure was rate of live birth (>=24 weeks gestational age). Generalized estimating equations were used to account for multiple cycles from the same recipient, adjusted a priori for recipient and donor age. Results Mean recipient serum P at ET was 25.5±10.1 ng/mL. Recipients with P<20 ng/mL at ET, despite P dose increases after ET, were less likely to achieve clinical pregnancy (RR= 0.75, 95 % CI=0.60-0.94, p=0.01) and live birth (RR=0.77, 95 % CI=0.60-0.98, p=0.04), as compared to those with P≥ 20 ng/mL. P dose increases were more often required in overweight and obese recipients. Conclusions Serum P levels on the day of ET in fresh donor IVF/ICSI cycles were positively correlated with clinical pregnancy and live birth rates. An increase in P dose after ET was insufficient to rescue pregnancy rates. Overweight and obese recipients may require higher initial doses of P supplementation. Future research is needed to define optimal serum P at ET and the interventions to achieve this target.
Obstetrics & Gynecology, 2011
To estimate the effect of body mass index (BMI) on oocyte and embryo parameters and cycle outcome... more To estimate the effect of body mass index (BMI) on oocyte and embryo parameters and cycle outcomes in women undergoing in vitro fertilization (IVF). METHODS: We evaluated a retrospective cohort of 1,721 women undergoing a first IVF cycle with fresh, autologous embryos between 2007 and 2010 in an academic infertility practice. Main outcome measures included number of mature and normally fertilized oocytes, embryo morphology, estradiol on the day of human chorionic gonadotropin administration, clinical pregnancy, spontaneous abortion, and live birth. We performed multivariable analyses, adjusting for potential confounders, including age at cycle start, infertility diagnosis, type of stimulation, total gonadotropin dose, use of intracytoplasmic sperm injection, and number of embryos transferred. RESULTS: Compared with women of normal BMI, women with class II (BMI 35-39.9) and III (BMI 40 or higher) obesity had fewer normally fertilized oocytes (9.3 compared with 7.6 and 7.7, P<.03) and lower estradiol levels (2,047 pg/mL compared with 1,498 and 1,361, P<.001) adjusting for age and despite similar numbers of mature oocytes. Odds of clinical pregnancy (odds ratio [OR] 0.50, 95% confidence interval [CI] 0.31-0.82) and live birth (OR 0.51, 95% CI 0.29-0.87) were 50% lower in women with class III obesity as compared with women of normal BMI. CONCLUSION: Obesity was associated with fewer normally fertilized oocytes, lower estradiol levels, and lower pregnancy and live birth rates. Infertile women requiring IVF should be encouraged to maintain a normal weight during treatment.
Molecular Human Reproduction, 2012
Diminished ovarian reserve (DOR) is a challenging diagnosis of infertility, as there are currentl... more Diminished ovarian reserve (DOR) is a challenging diagnosis of infertility, as there are currently no tests to predict who may become affected with this condition, or at what age. We designed the present study to compare the gene expression profile of membrana granulosa cells from young women affected with DOR with those from egg donors of similar age and to determine if distinct genetic patterns could be identified to provide insight into the etiology of DOR. Young women with DOR were identified based on FSH level in conjunction with poor follicular development during an IVF cycle (n ¼ 13). Egg donors with normal ovarian reserve (NOR) comprised the control group (n ¼ 13). Granulosa cells were collected following retrieval, RNA was extracted and microarray analysis was conducted to evaluate genetic differences between the groups. Confirmatory studies were undertaken with quantitative RT-PCR (qRT-PCR). Multiple significant differences in gene expression were observed between the DOR patients and egg donors. Two genes linked with ovarian function, anti-Mullerian hormone (AMH) and luteinizing hormone receptor (LHCGR), were further analyzed with qRT-PCR in all patients. The average expression of AMH was significantly higher in egg donors (adjusted P-value ¼ 0.01), and the average expression of LHCGR was significantly higher in DOR patients (adjusted P-value ¼ 0.005). Expression levels for four additional genes, progesterone receptor membrane component 2 (PGRMC2), prostaglandin E receptor 3 (subtype EP3) (PTGER3), steroidogenic acute regulatory protein (StAR), and StAR-related lipid transfer domain containing 4 (StarD4), were validated in a group consisting of five NOR and five DOR patients. We conclude that gene expression analysis has substantial potential to determine which young women may be affected with DOR. More importantly, our analysis suggests that DOR patients fall into two distinct subgroups based on gene expression profiles, indicating that different mechanisms may be involved during development of this pathology.
The Lancet Oncology, 2013
Background-Prior studies have documented decreased pregnancy rates and early menopause in female ... more Background-Prior studies have documented decreased pregnancy rates and early menopause in female cancer survivors; however, infertility rates and reproductive interventions have not been studied. This study investigates infertility and time to pregnancy among female childhood cancer
Journal of Clinical Oncology, 2014
Purpose Most research regarding fertility in young women with breast cancer has focused on long-t... more Purpose Most research regarding fertility in young women with breast cancer has focused on long-term survivors. Little is known about how fertility concerns affect treatment decisions or fertility preservation strategies at the time of initial cancer diagnosis. Patients and Methods As part of an ongoing prospective multicenter cohort study, we surveyed women with newly diagnosed early-stage breast cancer at age ≤ 40 years. The baseline survey included sociodemographic, medical, and treatment data as well as a modified Fertility Issues Survey, including fertility concern and preservation items. Univariable and multivariable modeling were used to investigate predictors of greater fertility concern. Results Among the first 620 eligible respondents included in this analysis, median age was 37 years (range, 17 to 40 years); 425 women (68%) discussed fertility issues with their physicians before starting therapy, and 319 (51%) were concerned about becoming infertile after treatment. Becau...
Human Reproduction, 2011
background: The FMR1 premutation is associated with overt primary ovarian insufficiency (POI). Ho... more background: The FMR1 premutation is associated with overt primary ovarian insufficiency (POI). However, its prevalence in women with occult POI (i.e. menstrual cycles, but impaired ovarian response) has not been examined. We hypothesized that both the FMR1 premutation and intermediate allele is more frequent in infertile women with occult POI than in controls, and that a repeat length cutoff might predict occult POI. methods: All subjects were menstruating women ,42 years old and with no family history of unexplained mental retardation, autism or fragile X syndrome. Cases had occult POI defined by elevated FSH or poor response to gonadotrophin therapy (n ¼ 535). Control subjects (n ¼ 521) had infertility from other causes or were oocyte donors. Prevalence of the FMR1 premutation and intermediate alleles was examined and allele length was compared between controls and women with occult POI. results: The frequency of the premutation (7/535 versus 1/521; P , 0.05) and intermediate alleles (17/535 versus 7/521; P , 0.05) was higher in women with occult POI than in controls. The allele with the greatest number of CGG repeats was longer in women with occult POI compared with controls (32.7 + 7.1 versus 31.6 + 4.3; P , 0.01). A receiver operating characteristic curve examining repeat length as a test for occult POI had an area of 0.56 + 0.02 (P , 0.01). A repeat cutoff of 45 had a specificity of 98%, but a sensitivity of only 5% to identify occult POI. The positive predictive value was only 21% for a fertility population that has 22% of its patients with occult POI. conclusions: The data suggest that FMR1 premutations and intermediate alleles are increased in women with occult POI. Thus, FMR1 testing should be performed in these women as some will have fragile X-associated POI. Although the FMR1 repeat lengths were longer in women with occult POI, the data do not support the use of a repeat length cutoff to predict occult POI.
Journal of Assisted Reproduction and Genetics, 2000
Purpose: Basal follicle-stimulating hormone (FSH) and ageare predictors of successful outcome in ... more Purpose: Basal follicle-stimulating hormone (FSH) and ageare predictors of successful outcome in in vitro fertilization(IVF). More recently, the clomiphene citrate challenge test(CCCT) has been proposed as a better way to predict IVFoutcome than FSH alone. The purpose of this study was todetermine which indicator of ovarian reserve—basal(day 3) FSH or the CCCT—is the better predictor of IVF successin the critical
Fertility and Sterility, 2013
Objective: To compare the efficacy and safety of luteal phase support in IVF with a progesterone ... more Objective: To compare the efficacy and safety of luteal phase support in IVF with a progesterone (P) vaginal ring or gel (VR or VG). Design: Prospective, randomized, single-blind, multicenter, phase III clinical trial (ClinicalTrials.gov identifier: NCT00615251). Setting: Nineteen private and three academic high-volume U.S. IVF centers. Patient(s): One thousand two hundred ninety-seven infertile patients were randomized to a weekly P VR (n ¼ 646) or a daily P 8% VG (n ¼ 651). Intervention(s): IVF was performed per site-specific protocols. The day after egg retrieval, patients were randomized and began VR or VG therapy, which continued for up to 10 weeks' gestation. Main Outcome Measure(s): Clinical pregnancy rates at 8 and 12 weeks of pregnancy; rates of biochemical pregnancy, live birth, spontaneous abortion, ectopic pregnancy, and cycle cancellation; and safety and tolerability were secondary measures. Result(s): Clinical pregnancy rates at 8 and 12 weeks were high and comparable between groups: 48.0% for VR and 47.2% for VG at week 8 and 46.4% (VR) and 45.2% (VG) at week 12. Live-birth rates were 45% (VR) and 43% (VG). Adverse event profiles were similar between groups. Conclusion(s): The weekly P VR provided similar pregnancy rates to the daily VG, with no major differences in safety. (Fertil Steril Ò 2013;99:1543-9. Ó2013 by American Society for Reproductive Medicine.
Fertility and Sterility, 2005
Objective: To determine whether peripheral blood mononuclear cell (PBMC) secretion of T-helper (T... more Objective: To determine whether peripheral blood mononuclear cell (PBMC) secretion of T-helper (Th)-1 type cytokines and Th-2 and Th-3 type cytokines in women undergoing in vitro fertilization-embryo transfer (IVF-ET) is associated with therapeutic failure and success, respectively. Design: Cohort study. Setting: Academic medical center. Patient(s): One hundred one women undergoing IVF-ET and 19 fertile controls. Intervention(s): Peripheral blood was obtained from women undergoing IVF-ET before oocyte retrieval and from 19 nonpregnant fertile controls. The PBMCs were cultured in the presence or absence of a protein extract from either a trophoblast cell line or sperm membrane. Main Outcome Measure(s): Supernatants from PBMC cultures were tested by enzyme-linked immunoabsorbent assay (ELISA) for the Th-1 type cytokines tumor necrosis factor-alpha (TNF)-␣) and interferon-gamma (IFN)-␥), the Th-2 type cytokines interleukin (IL)-6 and IL-10, and the Th-3 type cytokine transforming growth factor (TGF)-1. Result(s): Levels of IL-6 and IL-10 were significantly higher in controls than in infertile women with endometriosis, and levels of IL-10 were higher in controls than in women with unexplained infertility. No differences were found in unstimulated levels of TNF-␣, IFN-␥, or TGF-1 between infertile patients and controls. In trophoblast-stimulated PBMC cultures, levels of TGF-1 were significantly lower in subjects who experienced failed compared with ongoing pregnancies. Conclusion(s): Baseline PBMC secretion of IL-6 and IL-10 is higher in fertile controls than in women with endometriosis, and IL-10 secretion is also higher than in women with unexplained infertility. Trophoblaststimulated PBMC secretion of TGF-1 is positively associated with the establishment of successful pregnancy in women undergoing IVF-ET. Our study provides novel evidence to support a faciliatory role of Th-2 and Th-3 type responses to trophoblast in early pregnancy.
Fertility and Sterility, 2003
confounding age factor, pregnant cycles with basal FSH Ն 15 mIU/ml had a significant increased ri... more confounding age factor, pregnant cycles with basal FSH Ն 15 mIU/ml had a significant increased risk of PPL (pϽ0.05). Cause of infertility, peak E 2 on hCG day, No. of ET, and fertilization method were not associated with the risk of PPL. After adjusting for possible confounding factors with multivariate logistic regression, female age (pϭ0.04), basal E 2 (pϭ0.001), endometrial thickness (pϭ0.02) remained significant risk factors for PPL, but female age (pϭ0.001) was the only significant risk factor for clinical abortion following ART. Conclusion: This study demonstrated that female age, elevated basal estradiol, elevated basal FSH, thin endometrium are associated with an increased risk of preclinical pregnancy loss following ART. P-145 IVF success in patients 41 years and older with an elevated day 3 FSH is impacted by the number of cycle attempts.
Fertility and Sterility, 2002
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Papers by Elizabeth Ginsburg