Predictors and outcomes in breast cancer patients who did or did not pursue fertility preservation.

PURPOSE: 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). METHODS: 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. RESULTS: 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 E2 level or total gonadotropin dose. Likelihood of pursuing FP was primarily a function of age and parity, and was not affected by breast cancer stage. To date, 21 have used cryopreserved specimens, and 13 (62%) had a live birth. CONCLUSIONS: FP is safe and effective in breast cancer patients, regardless of receptor status; E2 elevations and the 2-week delay in treatment start are unlikely to be clinically significant. These findings are unique in that our institution does not use concomitant letrozole during stimulation to minimize E2 elevations in breast cancer patients.

Long-term outcomes in cancer patients who did or did not pursue fertility preservation.

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 χ2 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.

First-trimester bleeding and twin pregnancy outcomes after in vitro fertilization.

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.

Psychological Counseling of Female Fertility Preservation Patients.

Young cancer patients are increasingly interested in preserving their fertility prior to undergoing gonadotoxic therapies. Although the medical safety and treatment protocols for fertility preservation have been well documented, limited research has addressed the emotional issues that arise in fertility preservation patients. We briefly review the literature on the psychosocial issues in adult female fertility preservation treatment and describe our experiences within this patient population. Our findings suggest that several important issues to be addressed during the psychological counseling of adult female fertility preservation patients include: (1) preexisting psychological distress in patients undergoing treatment, (2) choice of fertility preservation strategy in the face of an uncertain relationship future, (3) decision making regarding use of third-party reproduction (e.g., sperm/egg donation, gestational surrogacy), (4) treatment expectations regarding pregnancy and miscarriage, (5) ethical issues related to treatment including the creation, cryopreservation, and disposition of embryos/oocytes, and (6) decision regret from patients who declined fertility preservation.

Prospective study of depression and anxiety in female fertility preservation and infertility patients.

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.

The progressive simplification of the infertility evaluation.

OBJECTIVE: 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. CONCLUSIONS: 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. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: 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.

Randomized controlled trial: effects of acupuncture on pregnancy rates in women undergoing in vitro fertilization.

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 <38 years old undergoing IVF with or without intracytoplasmic sperm injection. 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.

Fertility preservation for female cancer patients: early clinical experience.

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.

Studies of gene expression in human cumulus cells indicate pentraxin 3 as a possible marker for oocyte quality.

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.

Increased endometrial thickness is associated with improved treatment outcome for selected patients undergoing in vitro fertilization-embryo transfer.

OBJECTIVE: 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. DESIGN: Retrospective study. SETTING: A university-affiliated clinical IVF center. PATIENT(S): Patients undergoing IVF-embryo transfer with their own oocytes. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): 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. RESULT(S): 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. CONCLUSION(S): Increased endometrial thickness was associated with improved treatment outcome, but this association was dependent on patient age, duration of ovarian stimulation, and embryo quality.

Endometrial biopsy should be abandoned as a routine component of the infertility evaluation.

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.

Delay of embryo transfer to day 5 results in decreased initial serum beta-human chorionic gonadotropin levels.

OBJECTIVE: To investigate the impact of delaying the transfer of in vitro fertilized embryos to day 5 on embryo development by comparing serum beta-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 beta-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 beta-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 beta-hCG concentrations were 162 +/- 105 (n = 52) or 109 +/- 55 (n = 49) after day 3 or day 5 transfers, respectively. The percentage increases in beta-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 beta-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.

Relationship between peak serum estradiol levels and treatment outcome in in vitro fertilization cycles after embryo transfer on day 3 or day 5.

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.