Effect of randomized serum progesterone concentration on secretory endometrial histologic development and gene expression.

STUDY QUESTION: What doses of secretory phase progesterone (P) in women are associated with altered endometrial structure and/or function? SUMMARY ANSWER: Consistently delayed histological maturation was seen at the lowest tested daily P dose (2.5 mg), whereas consistently altered functional response, as reflected by microarray analysis of gene expression was seen at both the 5 and 2.5 mg doses. WHAT IS KNOWN ALREADY: Progesterone is absolutely required for normal embryo implantation and pregnancy survival. Progesterone supplementation is beneficial in ART cycles. STUDY DESIGN, SIZE, DURATION: In this case-control experimental trial, 46 healthy young female volunteers (age 19-34) underwent a single modeled endometrial cycle after GnRH down-regulation or monitored in natural cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: In a university hospital, modeled cycles were obtained by GnRH agonist down-regulation, transdermal estradiol (E2) (0.2 mg/d), and daily injections of P in oil for 10 days: 2.5 mg (n = 6), 5 mg (n = 6), 10 mg (n = 12) or 40 mg (n = 12), after the 10th day of E2. Ten healthy, ovulatory women were used as controls. Endometrial biopsies were obtained on the 10th day of P exposure, or urinary LH surge (in controls). Analysis included histological dating, serum progesterone levels, microarray analysis of the whole genome, RT-PCR, western blot and comparison with the GEO database. MAIN RESULTS AND THE ROLE OF CHANCE: In endometrial biopsies, a morphological delay appears in the 2.5 mg/day of P group. Higher sub-physiological levels of P (≥5 mg/day) resulted in normal histology, but aberrant gene expression. P levels required for consistent histological delay were lower than those in all ovulatory women. Gene expression abnormalities occurred at higher sub-physiological P concentrations, without a change in histology, a functional-morphological disassociation. The expression of some endometrial receptivity-associated genes appeared multiphasic, with peak or nadir of mean or median expression levels between the lowest and highest doses, suggesting sustained supraphysiological doses seen in ART treatment cycles may not be optimal. LARGE SCALE DATA: GEO DataSets ID: 200056980; GSE 56980. LIMITATIONS, REASONS FOR CAUTION: These results were obtained in fertile women, who may respond differently from infertile subjects. WIDER IMPLICATIONS OF THE FINDINGS: The dose of P required for normal endometrial structure (5 mg/day) corresponds to a P concentration well below that seen in ovulatory women, suggesting that persistently delayed mid-secretory histology cannot be solely due to inadequate P concentrations in an ovulatory cycle. Endometrial gene expression is differentially regulated by different doses of progesterone. The apparent multiphasic response of some genes to P dose suggests the possibility that P concentration kinetics may play a role in normal endometrial preparation for receptivity. These findings strongly confirm that histologic development is not a reliable measure of endometrial P action. STUDY FUNDING/COMPETING INTEREST(S): Supported by The Eunice Kennedy Shriver National Institute for Child Health and Disease, National Institute of Health, USA (NICHD/NIH) (R01HD067721 and U54HD30476; SLY and BAL) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 240239/2012-1 (RFS). All authors have no competing interests.

Fertility preservation consultation for women with cancer: are we helping patients make high-quality decisions?

To investigate the efficacy of the current fertility preservation consultation process in patients' decision-making and socio-demographic and cognitive factors that may affect patients' decision-making, a prospective pilot survey was conducted at university-based IVF centres and included women aged 18-43 years seen for fertility preservation between April 2009 and December 2010. Patients' views on consultation and decision-making about fertility preservation were measured. Among 52 women who completed the survey, more than half (52%) requested their consultation. All patients answered that consultation was a helpful resource of information, and 73% made their decision about treatment after consultation. Decisional conflict was lower in patients who felt strongly that they were given opportunities to ask questions during the consultation (P=0.001) and higher those who reported that cost was strongly influential in the treatment decision (P<0.001) and who did not receive treatment (P<0.001). Although consultation appeared to play a critical role in patients' decision-making about fertility preservation, the referral rate for consultation by oncologists is still poor. Decision-making appears to be significantly impaired in patients grappling with financial concerns and when the opportunity to ask questions is not felt to be sufficient.

Robotic resection of adnexal masses during pregnancy.

OBJECTIVE: To characterize the safety and feasibility of robotic adnexal surgery during pregnancy, and to compare surgical and obstetric outcomes for robotic versus laparoscopic treatment of adnexal masses during pregnancy. STUDY DESIGN: A retrospective cohort study of all cases of robotic resection of adnexal masses in gravid patients performed at our institution between 2006 and 2009 compared with 50 consecutive historic laparoscopic controls performed between 1999 and 2007. RESULTS: During the study period, 19 parturients underwent planned robotic resection of adnexal masses, all of which were uncomplicated. Compared with 50 consecutive laparoscopic controls, no differences in operative time, conversion to laparotomy, intraoperative or postoperative complications, or observed obstetric outcomes were apparent. The robotic cohort had a significantly shorter length of hospital stay (p < 0.01) and estimated blood loss (p = 0.02). CONCLUSION: Robotic resection of adnexal masses during pregnancy appears both safe and feasible, with similar surgical outcomes when compared with a historic laparoscopic cohort.

Trends of socioeconomic disparities in referral patterns for fertility preservation consultation.

BACKGROUND: While oncologists are aware that cancer treatments may impact fertility, referral rates for fertility preservation consultation (FPC) remain poor. The goal of this study was to identify predictors associated with FPC referral. METHODS: This is a retrospective, cohort study of women aged 18-42 years diagnosed with a new breast, gynecologic, hematologic or gastrointestinal cancer at our institution between January 2008 and May 2010. Exclusion criteria included history of permanent sterilization, documentation of no desire for future children, stage IV disease, short interval (<4 days) between diagnosis and treatment and treatment that posed no threat to fertility. Demographic, socioeconomic and cancer variables were evaluated with respect to FPC. Logistic regression was used to determine the odds of referral for FPC based on specified predictors. RESULTS: One hundred and ninety-nine patients were eligible for FPC and of those, 41 received FPC (20.6%). Women with breast cancer were 10 times more likely to receive FPC compared with other cancer diagnoses [odds ratio (OR) 10.1; 95% confidence interval (CI) 3.8-26.8]. The odds of FPC referral were approximately two times higher for Caucasian women (OR 2.4; 95% CI 0.9-6.2), three times higher for age <35 years (OR 3.3; 95% CI 1.4-7.7) and four times higher in nulliparous women (OR 4.6; 95% CI 1.9-11.3). There was no association between BMI, income, distance to our institution, being in a relationship and referral for FPC. CONCLUSIONS: Overall referral rates for FPC are low, and there appear to be significant discrepancies in referral based on ethnicity, age, parity and cancer type. This highlights a need for further provider education and awareness across all oncologic disciplines.

The current fertility preservation consultation model: are we adequately informing cancer patients of their options?

BACKGROUND: There is very limited information about the amount of information that cancer patients retain after a fertility preservation (FP) consultation (FPC). Our objective was to assess patients' knowledge following FPC and to examine predictors of increased knowledge. METHODS: We conducted a multi-center, cross-sectional, web-based survey at academic IVF centers, including women aged 18-43 years seen for comprehensive FPC between April 2009 and December 2010. The primary outcome measure was a knowledge score designed to assess comprehension of FP options. Analysis was performed to assess which patient variables were associated with higher knowledge scores. A 13-item knowledge tool about FP was developed (Kuder-Richardson 20=0.64). RESULT(S): Among 90 eligible subjects, 66 were successfully contacted and 52 completed the survey (79% response rate). Participant's median age was 30.7 (interquartile range (IQR) 24.9-36.9) years and most were Caucasian, college graduates, nulliparous and in a committed relationship. The median knowledge post-FPC score was 6 (IQR: 5-9). Higher knowledge scores were associated with a college education, higher income, a primary diagnosis of breast cancer, additional contact with the FP specialist following the initial FPC and use of specific reference websites such as www.fertilehope.org. Parity, marital status and completion of FP treatment were not associated with knowledge scores. CONCLUSIONS: FP knowledge following comprehensive FPC remains limited. Modifications to the current single visit FPC, such as a standard follow-up visit or additional educational tools, may be needed to improve patient comprehension of complex FP treatment options. Further research is needed to validate the knowledge scale in broader populations of cancer patients receiving FPC.

Periconceptional changes in thyroid function: a longitudinal study.

BACKGROUND: Limitations in our current knowledge of normative physiologic changes in thyroid function during the periconception window narrow our ability to establish an optimal approach to screening and diagnosis of thyroid disease in pregnant women. The objective of this study was to characterize changes in thyroid function during the transition from the pre-pregnant to pregnant state in normal fertile women. METHODS: Women (N = 60) ages 30-42 years without a history of thyroid disease, who were planning pregnancy, were observed prospectively before and during early pregnancy. Thyroid function (thyroid stimulating hormone, TSH and free thyroxine, FT4) was measured before conception and between 6 and 9 weeks gestation. Pre-pregnancy samples were analyzed for thyroid antibodies. Bivariate analyses and longitudinal curves (general estimating equation models) were used to analyze changes in thyroid function during the periconception window by antibody status. RESULTS: Pre-pregnancy TSH values were significantly higher than early pregnancy TSH (p < 0.001), but FT4 values did not differ (p = 0.53). TSH declined as gestational age increased (P < 0.01). Thyroid antibody positive women had a higher pre-pregnancy TSH compared to antibody negative women (p < 0.01). Periconceptional change in thyroid function was more variable among women with antibodies (p < 0.001). 50% of women with elevated pre-pregnancy TSH values (TSH > 3.0 mIU/L) had normal TSH values (TSH < 2.5 mIU/L) in pregnancy. CONCLUSIONS: TSH values decline during the transition from pre-pregnancy to early pregnancy. The change in TSH appears to be less predictable in women with thyroid antibodies. Periconceptional changes in thyroid function should be considered in formulating prenatal thyroid screening guidelines.

Management of a persistent adnexal mass in pregnancy: what is the ideal surgical approach?

STUDY OBJECTIVE: To compare short-term and pregnancy-related outcomes of laparoscopy with laparotomy for management of a persistent second-trimester adnexal mass. DESIGN: Retrospective cohort study of pregnant women at 14 weeks or more of gestation undergoing laparoscopy or laparotomy for management of an adnexal mass (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: Women of reproductive age with a persistent adnexal mass at 14 weeks or more of gestation. INTERVENTION: Removal of adnexal mass via laparoscopy or laparotomy. MEASUREMENTS AND MAIN RESULTS: Between 1990 and 2008, 101 pregnant women underwent treatment of a persistent adnexal mass at 14 weeks or more of gestation at our institution. Fifty women underwent laparoscopy, and 51 underwent laparotomy. Similar demographic and adnexal mass characteristics were identified between the 2 surgical groups. Eight patients in the laparotomy group experienced postoperative complications, compared with none in the laparoscopy group (p < .02). Mean surgical estimated blood loss and length of hospital stay were significantly less in the laparoscopy group compared with the laparotomy group: 17.5 mL vs 100 mL (p < .001) and 0.7 days vs 2.78 days (p < .001), respectively. There were no observed differences in pregnancy-related outcomes between the 2 groups. CONCLUSION: Minimally invasive surgery is a reasonable approach to management of a second-trimester adnexal mass in gravid women. Laparoscopy enables a shorter hospital stay, decreased blood loss, and fewer postoperative complications without seeming to have a negative effect on pregnancy-related outcomes. While these findings are reassuring, larger studies are encouraged to continue to evaluate this issue.

Fertility preservation: a pilot study to assess previsit patient knowledge quantitatively.

OBJECTIVE: To provide a quantitative assessment of patient knowledge about fertility and fertility preservation treatment options before the initial fertility preservation consultation at a university-based fertility preservation center. DESIGN: Prospective pilot survey containing 13 items assessing patient knowledge about fertility preservation, including the available treatment options and their requirements, success rates, and associated risks. SETTING: University-based IVF center. PATIENT(S): Women aged 18 to 41 years with illnesses requiring treatments posing a serious threat to future fertility who were referred for fertility preservation consultation between April 2009 and June 2010. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Knowledge score. RESULT(S): Forty-one eligible patients were identified, and all completed surveys before their consultation. A knowledge score was generated for each patient with 1 point awarded for each correct answer. Overall, patients had poor previsit fertility preservation knowledge (mean score 5.9±2.7). Higher knowledge scores were correlated with personal experience with infertility and previous exposure to fertility preservation treatment information. There was no correlation between knowledge score and age, relationship status, pregnancy history, education, or income. CONCLUSION(S): Patients seen for fertility preservation consultation at our university-based center generally tend to be in their early 30s, white, well educated, and married. Previsit knowledge about fertility preservation treatment options was poor and did not correlate with age, education, and relationship status.