Endocrine disruptor & nutritional effects of heavy metals in ovarian hyperstimulation.

PURPOSE: There is increasing concern that environmental chemicals have a direct effect on fertility. Heavy metals such as mercury have been shown to affect various organ systems in humans including nervous system and skin, however they could also act as endocrine disrupting chemicals adversely affecting fertility. Metals such as zinc and selenium are essential micronutrients with diverse functions that may be important for reproductive outcomes. We measured mercury, zinc and selenium levels in the hair, a reliable reflection of long term environmental exposure and dietary status, to correlate with the outcome of ovarian hyperstimulation for in vitro fertilisation (IVF) treatment. METHODS: We analysed the hair of 30 subfertile women for mercury, zinc and selenium using inductively coupled mass spectrometry. Each woman underwent one cycle of IVF treatment. Correlation between the levels of these trace metals and treatment outcomes was investigated. RESULTS: Thirty women were recruited with mean (±SD) age of 32.7(4.4) years and BMI of 25.4(5.0)kg/m(2). Hair mercury concentration showed a negative correlation with oocyte yield (p < 0.05,ßcoefficient 0.38) and follicle number (p = 0.03,ß coefficient0.19) after ovarian stimulation. Zinc and selenium levels in hair correlated positively with oocyte yield after ovarian stimulation (p < 0.05,ß coefficient0.15) and (p = 0.03,ß coefficient0.21) respectively. Selenium levels in hair correlated significantly with follicle number following stimulation (p = 0.04, ßcoefficient0.22). There was no correlation between mercury, zinc and selenium in hair and their corresponding serum levels. CONCLUSION: These data suggest that mercury had a deleterious effect whilst there was a positive effect for zinc and selenium in the ovarian response to gonadotrophin therapy for IVF. Hair analysis offers a novel method of investigating the impact of long-term exposure to endocrine disruptors and nutritional status on reproductive outcomes.

Viewing ultrasound scan images prior to termination of pregnancy: choice for women or conflict for ultrasonographers?

Establishing pregnancy location is key to minimising the risks of abortion, and establishing gestational age optimises women's choice of procedure and timing. There is limited information in UK practice about the views of women having an ultrasound before an abortion with regards to whether they would wish to see the scan image of their fetus. We therefore surveyed the views of women having pre-abortion ultrasound scans and the views of ultrasonographers, using self-completed anonymous questionnaires. Responses were available for analysis from 191 women aged 16 to over 45. A total of 25 (13%) women had seen their scan. Of those who did not see their scan, 40 (24%) said they would have liked to see it, to aid their decision-making, as a right, or out of curiosity. Nine out of 17 ultrasonographers completed their questionnaires. Four ultrasonographers thought that women having scans before an abortion should see their scan images if they wished and another four thought they should not because of possible psychological effects. Their response also highlighted possible effects of such scans on those performing them. Given the choice, a larger number of women would like to see their scan images than actually ask. Women request to see their pre-abortion ultrasound images for their own individual reasons, which should be respected. Ultrasonographers may have conflict or ethical dilemmas when performing pre-abortion scans and they should be supported in identifying women for whom looking at their scan images would be of benefit.

Obstetrics and gynaecology trainees' knowledge of electrosurgical equipment.

Electrosurgical energy is potentially dangerous but is a very useful surgical tool. A survey was planned to assess the knowledge of electrosurgery among obstetrics and gynaecology trainees in the Yorkshire Deanery (training region). Questionnaires were given to trainees attending the Modular training programme and were collected on the same day. A total of 71 questionnaires were collected, which represents 62% of the 113 trainees in Yorkshire region: 39 participants were registrars; 27 senior house officers (SHO); four senior SHOs, and one Clinical Fellow. A total of 52% of trainees had only MRCOG Part 1 and 36% of trainees had MRCOG Part 2; 53% of trainees had attended a Basic Surgical Skills course and 10% of trainees were not aware that the 'blue pedal' is used for coagulation (all were SHO except one Specialist Registrar, SpR). A total of 71% of trainees answered incorrectly that coagulating current provides an initial high voltage peak that quickly dissipates, while cutting current provides a constant high energy waveform. Trainees who had attended a Basic Surgical Skills (BSS) course did not demonstrate better knowledge. Knowledge of electrosurgery therefore was found to be poor among obstetrics and gynaecology trainees. Attending a BSS course did not seem to improve it significantly. This study outlines a training need. Perhaps a refresher course in electrosurgery and more focussed training might be useful for trainees with a particular interest in operative gynaecology, to acquire the necessary information and skills.

Ultrasound appearance of the uterus in women over 60 years of age on tibolone: is it a SERM?

OBJECTIVES: To evaluate the effects of long-term tibolone on the endometria of asymptomatic women over the age of 60 years. METHODS: An observational study of the ultrasound appearance of the endometria of women aged 60 years or older taking long-term tibolone. Those found to have a double-layer endometrial thickness greater than 4 mm were offered endometrial biopsy. RESULTS: Seventeen asymptomatic patients with a mean age of 61 years (range 60-73 years) and an average duration of tibolone use of 5 years (range 3-12 years) were recruited. Seven patients (41%) showed a thickened endometrium of more than 4 mm. Three of these had an area of translucency in the subendometrial space. Of the ten women with an endometrial thickness of less than 4 mm, four showed the presence of subendometrial fluid. Hysteroscopy was performed in five out of the seven women, as two did not accept further investigations. In all five women, the endometrial cavity was reported as atrophic and the histology showed an inactive basal type. In two of the five cases examined histologically, there were additional changes suggesting endometrial polyp, although the samples were from macroscopically non-polypoid endometrium. DISCUSSION: Endometrial thickness is increased in 41% of elderly women on long-term treatment with tibolone. However, at hysteroscopy, the endometrium was uniformly atrophic. Similar finding have been described in women using selective estrogen receptor modulators and a similar mechanism of action of these drugs on the uterus should be considered.

Is previous aberrant reproductive outcome predictive of subsequently reduced fecundity?

BACKGROUND: Effect of past reproductive performance on subsequent fecundity is uncertain. METHODS: A total of 2983 consecutive pregnant women self-completed questionnaires about time to pregnancy (TTP), pregnancy planning, previous pregnancies, contraceptive use, age, and individual/lifestyle variables. Outcome measures were: TTP, conception rates (CR) and, subfecundity odds ratio (OR; with 95% confidence intervals) before and after each outcome of last pregnancy. RESULTS: After miscarriage, TTP was longer than before miscarriage [2.1 (1.4-3.0), P < 0.001] and than TTP after livebirth [OR = 2.1 (1.6-2.6), P < 0.001]. Also subfecundity OR after miscarriage increased [1.7 (1.2-2.4), 1.8 (1.2-2.5), P = 0.001, 0.002 respectively]. This effect was more evident in older and obese women. Compared with livebirth, time to ectopic pregnancy (EP) was longer [OR = 13.8 (1.8-108.5), P = 0.001] but TTP after EP was not significantly different. Subfecundity OR relative to livebirth were 12.8 (3.6-45.0) (P<0.001) before, and 3.9 (1.4-11.0) (P=0.01) after, EP. The CR after EP increased 3-fold (1.1-8.3) over those prior to EP. Time to the terminated pregnancies even without contraceptive failures was shorter than that to livebirth [OR = 0.5 (0.3-0.7), P = 0.001] and than TTP after termination [0.35 (0.1-0.8), P = 0.001]. Also subfecundity OR increased after termination [7.2 (1.8-29.7), P = 0.02]. CONCLUSIONS: Miscarriers should be counselled about short-term reduction in subsequent fecundity, and earlier investigations should be considered in those who have other potential risk factors for reduced fertility. Further studies are required to clarify the relatively favourable effect on fecundity following EP and the relative reduction in fecundity after termination of pregnancy.

A national study examining the effect of making emergency hormonal contraception available without prescription.

BACKGROUND: In January 2001, emergency hormonal contraception was made available for women over the age of 16 years directly from a pharmacist without prescription. It is of interest whether this change in the UK has led to any improvements or deterioration in the service provided for the women who need it. METHODS: Self- completed, anonymous questionnaires were distributed to women requesting emergency hormonal contraception through a single group of pharmacies located throughout England, Wales and Scotland. RESULTS: A total 419 women returned completed questionnaires. A greater proportion of women were able to take emergency contraception within 24 h when they obtained their tablets directly from a pharmacy without a prescription (64% versus 46%, P = 0.029). Women who obtained their drugs directly from the pharmacist were just as well informed, just as likely to arrange regular follow-up and generally preferred this system, although they disliked having to pay. CONCLUSION: Making emergency hormonal contraception available without prescription has improved services to women who need them, but these improvements are quantitatively minimal, preventing only five additional pregnancies per 10,000 users.

Is previous use of hormonal contraception associated with a detrimental effect on subsequent fecundity?

BACKGROUND: The effects of contraception on subsequent fecundity are yet to be substantiated. METHODS: A total of 2841 consecutive pregnant women in Hull and Sheffield completed questionnaires inquiring about time to pregnancy (TTP), contraceptive use, pregnancy planning, previous pregnancies, age and lifestyle characteristics of each partner. Outcome measures were mean TTP, conception probability and odds of subfecundity after discontinuing each contraceptive method. RESULTS: TTP following long-term combined oral contraceptive (COC), short-term intrauterine device (IUD) or any duration of injectable use were 2.0-, 1.6-, 3.0-fold longer than TTP after condom use, respectively. Within 6 months of discontinuing COC or injectable use, conception probabilities were 0.86 and 0.34, respectively, whereas those relevant to other methods were not significantly different. All levonorgestrel intrauterine system (IUS) users conceived within 1 month. Relative to condoms, odds of subfecundity after COC, injectable and short-term IUD use were 1.9, 5.5, 2.9, respectively. The effect of COC and injectables was stronger with long-term use, in older, obese or oligomenorrhoeic women. Similar results were obtained after adjustment for potential confounders. CONCLUSIONS: A significant reduction in fecundity occurs after COC, IUD or injectables, which is dependent on the duration of use. The effect of COC and injectables is evident in women with a potentially compromised ovarian function. Use of progesterone-only pills or IUS is not associated with a significant effect.

Electrical impedance measurements: an objective measure of prelabor cervical change.

OBJECTIVE: To investigate the use of electrical impedance measurements of the pregnant cervix as an objective measure of cervical favorability (Bishop score > or = 5). METHODS: A prospective study of 86 women, investigating electrical impedance measurements of the pregnant cervix at the time of induction of labor. Transfer electrical impedance measurements were made by placing a tetrapolar pencil probe of 8 mm in diameter on the surface of the cervix. A Bishop score was determined simultaneously. RESULTS: A mean resistivity (standard error of the mean) of 7.03 (6.01-8.04) omega(m) was measured for the unfavorable group and 5.34 (4.61-6.07) omega(m) for the favorable group. This was a statistically significant difference (p = 0.016). CONCLUSION: We highlight the ability of this safe, painless technique to differentiate the favorable from the unfavorable cervix at induction of labor.

Improving cycle control in progestogen-only contraceptive pill users by intermittent treatment with a new anti-progestogen.

BACKGROUND: The safety and efficacy of the anti-progestogen Org 31710 in improving cycle control in healthy women using the desogestrel progestogen-only pill was investigated in this randomized, double-blind, placebo-controlled study. METHODS: A total of 103 women using the 75 micro g desogestrel progestogen-only pill daily also received either 150 mg Org 31710 or placebo once every 28 days, starting on day 1, for a duration of 4-7 treatment cycles. RESULTS: The percentage of women with bleeding or spotting (B/S) every day in the placebo group was on average 30% during the whole treatment period and no days without reported B/S occurred. In contrast, a cyclic pattern was observed for the Org 31710 group; a peak incidence of B/S was observed on day 3 or 4 of each cycle, followed by a sharp decrease on cycle days 9-15. Compared with controls, less subjects in the Org 31710 group reported irregular, frequent or prolonged bleeding. These differences were clearly observed in the initial cycles, but were somewhat less pronounced during the later cycles of the treatment period. A relatively high incidence of B/S episodes starting in the second section of the cycle was also observed. CONCLUSION: The addition of Org 31710 once a month improved cycle control in women using daily treatment with 75 micro g desogestrel.

Transmyometrial embryo transfer and junctional zone contractions.

BACKGROUND: Embryo transfer is a crucial step in IVF-embryo transfer cycles. Several studies have explored transmyometrial embryo transfer, but although this procedure has several favourable characteristics, its role in assisted reproduction has not yet been established. Junctional zone (JZ) contractions during embryo transfer are associated with a negative outcome and factors which increase JZ contractions should be avoided. METHODS: In this study, we have investigated the effect of transmyometrial embryo transfer on JZ contractions. Ten patients with a previously difficult embryo transfer, or a difficult mock embryo transfer, underwent transmyometrial embryo transfer. Before and after this procedure a transvaginal ultrasound scan was performed and this was recorded on videotape for 5 min. The recordings were digitized and then analysed for JZ contractions. RESULTS: Transmyometrial embryo transfer causes a significant increase in JZ contractions. CONCLUSION: The increase in JZ contractions after transmyometrial embryo transfer forms a theoretical objection to this procedure. However, its alternative, a difficult transcervical embryo transfer, is also associated with an increase in JZ contractions. We therefore suggest a large prospective study to investigate the most effective method of embryo transfer in cases where a difficult transcervical embryo transfer is anticipated due to cervical factors.

Ovarian function during and after treatment with the new progestagen Org 30659.

OBJECTIVE: To evaluate ovarian function during 21 days of oral administration of different doses of Org 30659, a novel selective progestagenic steroid. DESIGN: Randomized, double-blind, dose-finding study. SETTINGS: Three centers in Austria, Sweden, and the United Kingdom. PARTICIPANTS: Eighty-one healthy women 19-40 years of age with regular ovulatory cycles. INTERVENTION: Daily oral administration of 0.060, 0.120, 0.180, or 0.240 mg of Org 30659, or 0.075 mg desogestrel (reference group), for 21 days. MAIN OUTCOME MEASURE(S): Once-daily measurements of follicular diameter and 17-beta estradiol, progesterone, FSH, and LH levels. RESULT(S): Daily treatment with Org 30659 for 21 days caused dose-dependent suppression of ovarian activity. No ovulation was observed in any study group. On average, ovulation returned 16.5 to 22.1 days after treatment. The effects of desogestrel, 0.075 mg, were similar to those of 0.060 and 0.120 mg of Org 30659. All doses were well tolerated, as shown by the type of side effects that occurred, the absence of an effect on physical and laboratory findings, and the low rate of study discontinuation. CONCLUSION(S): Daily oral administration of 0.060-0.240 mg of Org 30659 suppresses ovarian function to a level sufficient to inhibit ovulation. This effect is dose-dependent, and the suppressive effect is readily reversible at all doses tested. Org 30659 can thus be safely administered orally for 21 days to healthy female volunteers in a dosage of 0.060 mg/d to 0.240 mg/d.

Induction of lactation in the intended mother of a surrogate pregnancy: case report.

A case of a successful induction of lactation in a commissioning mother of a surrogate pregnancy is reported. Induction of lactation was achieved with oral metoclopramide which was well tolerated. Alternative methods to induce lactation are reviewed. The advantages of breast-feeding and the relative ease with which lactation can be induced after a surrogate pregnancy would suggest that this could be offered to all commissioning mothers.

Single monthly administration of the anti-progestagen Org 31710 in users of the 75 microg desogestrel progestagen-only pill: effects on pituitary-ovarian activity.

Endocrine and ultrasound effects were studied of an intermittent (every 28 days) oral administration of 150 mg of the anti-progestagen Org 31710 during the continued daily use of 75 microg desogestrel (DSG) for progestagen-only contraception. A randomized, double-blind, placebo-controlled two-centre study was conducted in 50 healthy volunteers. Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), oestradiol and progesterone concentrations, and follicle number and size were studied, as well as endometrial thickness, which was assessed by transvaginal sonography at least twice weekly during a single medication cycle (cycle 3-5). Forty-eight women were evaluated (Org 31710, n = 25; placebo, n = 23). Seven ovulations were observed in the treated group versus none in the placebo group. LH concentrations were higher on days 9 and 11 and oestradiol concentrations lower on day 3 in the treated group, irrespective of whether ovulation occurred. No parameter could predict ovulation. Endometrial thickness was greater on cycle days 7-13 and 19 in the treated group. However, within the Org 31710 group, no significant differences were found in volunteers who did or did not ovulate. Observed differences may be attributed to a competitive effect of Org 31710 with progestagen-induced suppression of the pituitary-ovarian axis, altered oestradiol feedback mechanisms, and/or altered receptor availability.

Histological analysis of the uterine junctional zone as seen by transvaginal ultrasound.

OBJECTIVE: This study aimed to investigate the histology of the subendometrial halo, the junctional zone between the endometrium and myometrium. METHODS: Thirteen ex vivo uteri removed for treatment of menorrhagia were studied. In each case, the subendometrial halo, as seen by transvaginal ultrasound, was marked using a Nottingham breast location biopsy needle. A standard histological examination was performed. Full thickness blocks of the anterior uterine wall were taken and standard serial 5-micron tissue sections were prepared from each block. Subsequent morphometric analysis followed staining with Feulgen reagent, using a CAS 200D quantitative image analysis system. Additionally, anti-CD31, an antibody stain for vascular endothelium, was used. RESULTS: The histological examination showed the subendometrial halo to consist of apparently normal myometrium. Morphometric analysis demonstrated a greater total nuclear area in the subendometrial halo than the outer myometrium, but no difference in individual nuclear size between the two zones. CD31 stained a greater total area in the inner myometrium. CONCLUSIONS: These results suggest that the subendometrial halo is a distinct compartment of the myometrium comprising tightly packed muscle cells with an increased vascularity. Such architecture would increase the density of this tissue layer, altering its acoustic impedance, and account for its echopenic appearance on ultrasound.

Junctional zone contractions and embryo transfer: is it safe to use a tenaculum?

Applying a tenaculum to the cervix is a common practice when the correction of uterine position prior to embryo transfer is required. Our study was designed to assess junctional zone contractility before and after this procedure in 20 patients at the time of mock embryo transfer (mid-luteal phase, at commencement of down-regulation). Real-time transvaginal ultrasound and computer technology was used to evaluate the contraction pattern and frequency. When a tenaculum was applied, the total number of contractions, the number of cervico-fundal, random and opposing contractions all increased significantly (P values 0.0003, 0.005, 0. 001 and 0.007 respectively). Eleven women displayed cervico-fundal contractions, prominent opposing and random contractions were observed in all 20 patients and four patients generated fundo-cervical waves not seen in any case before stimulation with the instrument. In conclusion, manipulation with a tenaculum in the cervical area stimulates junctional zone contractions and is best avoided at the time of embryo transfer.