M.G.R. Hull

Delayed conception and active and passive smoking

OBJECTIVE To determine whether passive as well as active smoking by women or smoking by men is associated with delayed conception, after adjustment for confounding factors. DESIGN Population study of couples expecting a baby. Logistic regression was performed to identify factors associated with delayed conception. SETTING The Avon Health Authority area, United Kingdom. PATIENT(S) All couples expected to deliver between April 1991 and December 1992. INTERVENTION(S) Questionnaires administered early in pregnancy. MAIN OUTCOME MEASURE(S) Time taken to conceive, categorized as <6 months, 6-11 months, 1-3 years, and >3 years. RESULT(S) After correction for confounding factors, delayed conception was statistically significantly associated with both active smoking by the woman (odds ratio [OR] 1.23 [95% CI 0.98-1.49] for > 6 months and 1.54 [95% CI 1.19-2.01] for >12 months) and her exposure to passive smoking (OR 1.17 [95% CI 1.02-1.37] and 1.14 [95% CI 0.92-1.42]) compared with women with no exposure to tobacco smoke (referent). Heavy smoking by men was independently associated with delayed conception. In active smokers, the effect increased with the number of cigarettes. CONCLUSION(S) Smoking by men and passive and active smoking by women are associated with delayed conception.

The age-related decline in female fecundity: a quantitative controlled study of implanting capacity and survival of individual embryos after in vitro fertilization

OBJECTIVE To determine strictly comparable rates per embryo of implantation and birth of a baby related to the womans age, which would be representative of natural fertility at least in relative terms. DESIGN Comparative study of IVF-ET results controlling for confounding variables including cause and duration of infertility, history of previous pregnancy, hormonal treatment, rank cycle of treatment, and numbers of embryos transferred and available. SETTING University comprehensive fertility service. PATIENTS All couples (n = 561) in their first cycle of treatment reaching oocyte collection, women with normal uterus and ovulatory cycles, and men with normal sperm. INTERVENTIONS Standardized methods of pituitary desensitization, ovarian stimulation, and IVF-ET, and maximum of three embryos transferred. MAIN OUTCOME MEASURES Oocytes, pregnancies, and live births per cycle; fertilization and cleavage rates; embryo implantation and live baby rates. RESULTS The numbers of oocytes and consequent embryos declined with age but fertilization and cleavage rates rose slightly. Embryo implantation rates were reduced when no more than three embryos were available (9.3 percent), especially in women aged 35 to 39 years (6.2 percent) or older compared with four or more embryos (17.1 percent) but were equally low in all women over 40 years even with more embryos (6.1 percent). In the age bands 25 to 29, 30 to 34, 35 to 39, and 40 to 44 years, the rates per embryo of implantation were 18.2 percent, 16.1 percent, 15.3 percent, and 6.1 percent, respectively, and of a live baby were 15.7 percent, 12.1 percent, 12.0 percent, and 3.5 percent. CONCLUSIONS Embryo implanting ability and survival decline gradually after 30 years of age, but by more than two thirds after 40 years and in younger women with reduced ovarian capacity.

The diagnosis of polycystic ovaries in women with oligo‐amenorrhoea: predictive power of endocrine tests

The ability of several endocrine tests to distinguish between women with and without polycystic ovaries (PCO) has been studied prospectively in a series of 65 patients with functional oligo‐amenorrhoea using ultrasonography as a reference test. In terms of overall diagnostic accuracy, the free androgen Index (FAI) (94%) and the progestogen challenge (89%) gave similar results (CI =–5 to 15%) but both were significantly better than all the other tests including measurement of serum LH (69%), total testosterone (71%) and androstenedlone (74%) (minimum CI = 6 to 23%). The FAI together with LH measurement was the most accurate of the combinations (97%) but this was not significantly better than the best of the combinations Incorporating the progestogen challenge (92%; CI =–3% to 13%). Given the limited availability of the assay for SHBG, these results show that assessment of oestrogen state is a useful method for categorizing patients with functional oligo‐amenorrhoea

Pain after laparoscopy related to posture and ring versus clip sterilization.

Summary. In an attempt to reduce pain after laparoscopy, presumed to be due to persistence of CO2 in the peritoneal cavity especially under the diaphragm, women were kept 30° head down for 30 min immediately after operation. By random selection 67 treated patients were compared with 64 kept flat, postoperative symptoms being recorded at fixed times for 3 days. Although tilting was found to be of no significant benefit there were two useful findings. In both groups there was a significant fall in the frequency of upper abdominal pain during the first postoperative night from about 53% to about 25%, followed by a rise after returning home on the first postoperative day to about 60% and only a slow fall in the next 2 days. The severity of pain followed the same pattern. Patients should be warned to expect increased pain on ambulation after leaving hospital. Also, there was doubling in lower abdominal pain during the first 6 h associated with the use of Falope rings for sterilization, compared with either Hulka clip sterilization or only diagnostic laparoscopy.

Stress and stress-related hormones during in-vitro fertilization treatment

Whether stress and infertility are linked as cause or consequence is unclear, and there is no consensus on the most appropriate methods for measuring stress in infertile women. To address this question, we measured changes in biochemical and questionnaire-based assessments of stress in infertile women. Median baseline, follicular phase and pre-operative serum prolactin (229, 311 and 457 mIU/l) cortisol (278, 369 and 496 nmol/l) and state anxiety score (38, 40 and 49) respectively all increased during stimulated in-vitro fertilization (IVF) treatment. There was no such increase in a control group having similar laparoscopic surgery unrelated to infertility, or in women having unstimulated IVF without laparoscopy, suggesting that anxiety levels are greatest in stimulated IVF, increase as a result of the treatment, and are adequately reflected by state anxiety scores. Baseline serum prolactin in unstimulated IVF (384 mIU/l) was significantly higher than control (177 mIU/l), although this was not reflected in serum cortisol or state anxiety score. Trait anxiety was constant within and between groups, suggesting that stress is not contributing greatly to the infertility. Women who achieved a pregnancy had similar state anxiety scores to those who failed, suggesting that the degree of anxiety observed during IVF treatment is unlikely to influence the chance of pregnancy. There was a trend towards lower trait anxiety in women who became pregnant, but the numbers were small.

Abdominal pain after laparoscopy: the value of a gas drain.

Summary. In an attempt to reduce pain after laparoscopy, a drain was left for 6 h in the peritoneal cavity through the umbilical incision to take advantage of visceral peristaltic and voluntary muscle movements to expel residual gas. In a randomized study 25 treated patients were compared with 28 controls. Use of the drain was found to approximately halve the frequency of pain throughout the first 2 postoperative days. The severity of pain was also significantly reduced in the first 6 h and after mobilization at home the next day when pain is usually at its worst.

Prognostic value of the postcoital test: prospective study based on time‐specific conception rates

Summary. Time‐specific conception rates were studied prospectively after a carefully validated post‐coital test (PCT) in a consecutive series of 80 ovulatory women without any pelvic or seminal cause for their previous infertility. The PCT was performed on endocervical mucus collected 6–18 h after intercourse. The definition of a negative result, indicated by the absence of forward‐moving sperm, depended on the finding being repeated in a second cycle and on the presence each time of fully developed mucus, indicated simply by its abundance, ductility and clarity. The time to conception was inversely related to the number of motile sperm seen. Simpler analysis showed a fivefold greater chance of conception associated with a positive compared with a negative PCT; after 2 years the cumulative conception rates were 84 and 16% respectively.

Clomiphene treatment for women with unexplained infertility: placebo-controlled study of hormonal responses and conception rates

One hundred and eighteen patients with unexplained infertility were treated with clomiphene (Clomid, Merrell) in a randomized placebo-controlled cross-over study lasting up to 3 months with each preparation. Compared with placebo, clomiphene led overall to a 66% increase in mid-luteal serum progesterone levels (from mean 43 nmol/l to 71 nmol/l, p less than 0.001) and a 53% rise in the 3-month cumulative conception rate (from 14.6% to 22.33%, p less than 0.05). The greatest relative increase in conception rates with clomiphene was in women with infertility lasting more than 3 years (3-month rates from 2.9% to 14.4%, p less than 0.05). Differences in conception rates were not related to the rises in progesterone, and there was no carryover effect of clomiphene into the following placebo cycles in terms of progesterone levels or conceptions. The findings suggest that couples with unexplained infertility of less than 3 years duration are essentially normal, but with more than 3 years duration there is often a subtle disorder of ovulation that is corrected by clomiphene therapy.

The value of artificial insemination with husband's semen in infertility due to failure of postcoital spermmucus penetration—controlled trial of treatment

Summary. Artificial insemination with husbands semen into the cervical canal and uterine cavity (high AIH) was assessed by a randomized controlled prospective study in 46 couples whose infertility was due to failure of sperm mucus penetration, as defined by negative postcoital tests, after excluding all interfering female factors and men with sperm density <1 × 106/ml. Seminal analysis was abnormal in 18 of the 46 men and sperm antibodies in semen were detected in 19 of the remaining 28 with normal seminal analysis. Overall, the cumulative conception rate after 6 months with AIH was 4·7 (SE 3·8)% and without treatment was 6·6 (SE 3·9)%. The results were unaffected by the findings on seminal analysis or by the presence or absence of sperm antibodies in semen. AIH appeared to be of no benefit.

1 Is endometriosis a disease

Summary Recent comparative studies and developments in our understanding of the pathogenesis and pathophysiology of endometriosis have led to increasing doubts about whether it should always be considered a disease. Widespread use of laparoscopy for gynaecological investigation and treatment, recognition of non-pigmented lesions which are more active than classical implants, and the documentation of microscopic lesions in visually normal peritoneum, have all resulted in an increase in the frequency with which endometriosis is diagnosed. Recent studies suggest a prevalence of up to 80% in women complaining of infertility or pelvic pain, but also in up to 22% of fertile asymptomatic women undergoing sterilization. Perhaps it is a normal physiological variant, being present in such a high proportion of the population. Circumstantial evidence suggests this may be so, and the results with placebo treatment in controlled trials suggest that endometriosis is self-limiting and will regress or disappear spontaneously in 58% of women. The frequency and severity of symptoms which are often presumed to result from endometriosis do not correlate with the extent or site of lesions. Most women are pain-free. There is no dysmenorrhoea in up to 77%, no dyspareunia in up to 70%, and no pelvic pain at all in up to 61% of women with endometriosis. The pathophysiology of pain related to endometriosis is not understood. There is no medical or conservative surgical treatment that is wholly effective for symptom relief, and there is considerable placebo benefit. All treatments have risks or side-effects, and recurrent symptoms will develop in up to 45% of women within 5 years. For these reasons treatment should only be used where endometriosis fulfils the criteria of a disease, showing signs of progression with tissue damage or physiological disturbance. Asymptomatic endometriosis without tissue damage should not be considered a disease and should not be treated. Treatment of pain associated with minor endometriosis, or prophylactic treatment to prevent progression, must be regarded as empirical and not the specific requirement to control what is a questionable disease.