Hormone receptor expression patterns in the endometrium of asymptomatic morbidly obese women before and after bariatric surgery

Objective

Obesity increases risk for endometrial neoplasia, but neither the pathophysiology nor the effects of weight loss on the risk are well established. We attempted to characterize the molecular profile of the endometrium of asymptomatic women with morbid obesity before and following bariatric surgery-induced weight loss.

Methods

59 asymptomatic, morbidly obese women underwent endometrial sampling before bariatric surgery; 46 (78%) of these returned one year later for re-biopsy (median weight loss of 41 kg). Duplicate samples from these specimens were scored for expression of estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), and Ki-67 by two independent, blinded pathologists using an H-score [staining intensity (0–3) × (percent of tissue involved)].

Results

The prevalence of hyperplasia pre-operatively was 7% overall and 10% among patients not on an anti-estrogen. ER H-scores were similar before and after surgery overall (median 190 and 196 respectively, p = 0.82), but patients with hyperplasia had higher pre-operative H-scores (median 256, p < 0.001) and experienced greater H-score drops, than those without hyperplasia (− 112 vs + 50, p = 0.028). In two patients with persistent hyperplasia at one year, ER H-scores fell to levels that were similar to those without pathology. One patient who developed hyperplasia during the study period had a rising ER H-score. Patients with hyperplasia had higher median PR H-scores pre-operatively (284 vs 188, p = 0.01), which normalized through greater drops (75 vs 0, p = 0.053). AR H-scores dropped significantly after surgery (13 vs 2, p = 0.015), but were similar between patients with and without hyperplasia (p = 0.33). Weight loss did not affect Ki-67 proliferation index.

Conclusion

Asymptomatic morbidly obese patients have a high prevalence of occult hyperplasia, characterized by relatively high hormone receptor expression. These profiles appear to normalize with weight loss and in advance of pathologically identifiable changes. These data suggest a potential role for screening this population as well as the possibility that weight loss may be a valid treatment strategy for risk reduction.     

Poor pregnancy outcome in women with type 1 diabetes is predicted by elevated HbA1c and spikes of high glucose values in the third trimester

Abstract

Objective: To analyse data from a randomised, controlled study of prandial insulin aspart versus human insulin, both with NPH insulin, in pregnant women with type 1 diabetes for potential factors predicting poor pregnancy outcomes.

Research design/method: Post hoc analysis including 91 subjects randomised prior to pregnancy with known outcome in early pregnancy and 259 subjects randomised prior to pregnancy/during pregnancy of <10 weeks’ gestation with known late-pregnancy outcomes. Poor early-pregnancy outcomes included fetal loss <22 gestational weeks and/or congenital malformation (n?=?18). Poor late-pregnancy outcomes included: composite endpoint including pre-eclampsia, preterm delivery and perinatal death (n?=?78); preterm delivery (n?=?63); and excessive fetal growth (n?=?88).

Results: 18 patients experienced a malformed/lost fetus in early pregnancy – none preceded by severe hypoglycaemia. Albuminuria in early pregnancy was a significant predictor of poor late-pregnancy outcome (composite endpoint; p?=?0.012). In the third trimester, elevated HbA_1c,?≥?1 plasma glucose (PG) measurement >11?mmol/L (198?mg/dL) and %PG values outside 3.9–7.0?mmol/L (70–126?mg/dL) were significant predictors of poor late-pregnancy outcomes (all p?<?0.05).

Conclusions: Elevated HbA_1c, high glucose spikes and out-of-range %PG in the third trimester, and albuminuria in early pregnancy, are associated with poor late-pregnancy outcomes.     

Exposure to high levels of luteinizing hormone and estradiol in the early follicular phase of gonadotropin-releasing hormone antagonist cycles is associated with a reduced chance of pregnancy

OBJECTIVE: To compare ongoing implantation rates under two different GnRH antagonist protocols. DESIGN: Randomized controlled trial. SETTING: Tertiary referral center. PATIENT(S): One hundred eleven women undergoing ovarian stimulation for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). INTERVENTION(S): Ovarian stimulation with 150 IU recombinant-FSH (rec-FSH) starting on day 2 of the cycle and GnRH antagonist starting either on day 6 of stimulation (fixed group) or when a follicle of > or = 15 mm was present after at least 5 days of stimulation (flexible group). In the flexible group, the rec-FSH dose was increased to 250 IU when the antagonist was initiated. MAIN OUTCOME MEASURE(S): Ongoing implantation and pregnancy rate. RESULT(S): In patients with no follicle of > or = 15 mm present on day 6 of stimulation, a significantly lower ongoing implantation rate was observed if the flexible scheme was applied as compared with the fixed scheme of administration (8.8% vs. 23.9%, respectively). Exposure of the genital tract to LH or E2 from initiation of stimulation to antagonist administration was able to distinguish between pregnant and nonpregnant patients in the population studied. CONCLUSION(S): High exposure of the genital tract to LH and E2 in the early follicular phase is associated with a reduced chance of pregnancy in cycles stimulated with recombinant FSH and GnRH antagonist for IVF/ICSI.     

Management of weight loss in obesity-associated male infertility: a spotlight on bariatric surgery

In recent years, there has been a paralleled increase between male obesity and infertility rates. Obesity is associated with impaired hypothalamic-pituitary-gonadal axis, aberrant semen parameters, and subfertility or infertility. Weight loss is strongly recommended for the management of obesity-associated infertility. Lifestyle modifications that include caloric restriction and increased physical activity have a short-lived impact. Bariatric surgery is a better and more durable weight loss alternative. Comprehensive information about the benefits of weight loss on obesity-associated male infertility following bariatric surgery is still emerging. In this review, we discuss the hormonal, physical and environmental mechanism contributing to obesity-associated infertility. We then assess weight loss approaches, which include lifestyle modification, medical and surgical approaches, that can improve fertility in obese men. This review focuses also on bariatric surgery for the management of obese men seeking fertility treatment. Anecdotal evidence suggesting that bariatric surgery can impair fertility is also discussed.     

The influence of infant birth weight on post partum stress incontinence in obese women

One hundred ninety four women with a Body Mass Index (BMI) of at least 30 kg/m² who were delivered vaginally between 01 10 93 and 30 09 95 at the obstetric department, Herning Central Hospital, were sent a postal questionnaire about stress incontinence. The response rate was 89.2%. In the heavy birth weight group (n=4000 g or more) stress incontinence increased from 10.6% before pregnancy to 34.0% post partum. In the low birth weight group 6.9% suffered from stressincontinence before pregnancy increasing to 30.6% post partum. There was no difference in the reporting of mixed or urge incontinence between the two groups. Received: 4 November 1996 / Accepted: 12 November 1996     

The midluteal decline in serum estradiol levels is drastic but not deleterious for implantation after in vitro fertilization and embryo transfer in patients with normal or high responses

OBJECTIVE: To determine the impact of the peak E(2) level and its midluteal decline on IVF-ET outcome in a group of normal- and high-responding patients. DESIGN: Retrospective analysis of IVF-ET data. SETTING: Tertiary-care, university-affiliated teaching hospital. PATIENT(S): A total of 100 patients aged 98% E(2) decline; however, the difference did not reach statistical significance. CONCLUSION(S): Multifactorial analysis refutes the negative role of supraphysiologic levels of E(2) on the day of hCG administration or its dramatic decline at the midluteal phase on the success rate after embryo transfer. A possibly increased rate of early spontaneous abortion in the high-response group warrants further verification.     

Potentiation of Reduced Uteroplacental Perfusion Pressure Hypertension in Pregnant Rabbits

Objective: We tested whether indomethacin (IND) potentiates the elevation of blood pressure induced by the reduction of the uteroplacental perfusion pressure (RUPP).

Methods: In pregnant rabbits on the 21st day of the 30-day gestation, the uteroplacental perfusion pressure was reduced by 68 ± 5% using a clip placed on the abdominal aorta below the renal arteries. IND suppositories (15 mg/kg each) were administered 1 and 2 days following surgery.

Results: After the second dose, MAP of IND-treated RUPP rabbits was higher (92 ± 9 mm Hg, n = 10) than in those receiving placebo (78 ± 12, n = 9, P <. 01). MAP of sham-operated pregnant rabbits with or without IND was 61 ± 9 and 58 ± 8 mm Hg, respectively (NS). Placebo-treated RUPP animals evidenced an enhanced urinary sodium excretion as compared to nor-motensive control rabbits receiving placebo (3.27 ± 0.69 mmol/kg/day vs. 1.49 ± 0.74, P <. 001). Enhanced urinary sodium excretion was blunted by IND in RUPP rabbits (1.25 ± 0.37, P <. 001).

Conclusion: (1) IND potentiates the hypertensive response induced by RUPP. (2) the reduction of urinary sodium excretion may be one of the several pharmacological effects of IND aggravating hypertension in this state.     

Weight six years after childbirth: A follow-up of obese women in a weight-gain restriction programmme

Objective

to compare weight development in an intervention group and a control group, six years after participation in a gestational weight-gain restriction programme.

Design

follow-up of a prospective intervention study.

Settings

antenatal care clinics.

Participants

a total of 129 women (88.4%) from the original intervention group and 166 women (88.8%) from the original control group.

Measurements

the women answered a study specific questionnaire, covering socio-demographic data and health- and weight status.

Findings

after adjusting for socio-demographic factors, the mean weight was lower (4.1 kg) among the women in the intervention group, compared to the controls (p=0.028). Furthermore, the mean weight change, e.g. the weight at the six year assessment compared with the weight at the start of the intervention at the first antenatal care visit, was greater in the intervention group than in the control group. The women in the intervention group had a larger mean weight change (−5.2 kg), e.g. weighed less than the women in the control group (−1.9 kg) (p=0.046). Mean weight change expressed in 5 kg classes also showed a significant difference between the two groups (p=0.030).

Key conclusions

the results indicate that attending a gestational weight-gain-restriction programme can have a positive effect on weight up to six years after the intervention.

Implication for practise

a restrictive gestational weight gain can result in a positive weight development during the first years after childbirth. It might provide both short- and long term medical health benefits for the mother as well as the child.