Prognostic capacity of transvaginal hydrolaparoscopy to predict spontaneous pregnancy.

BACKGROUND: In 1998, transvaginal hydrolaparoscopy (THL) was introduced as a new outpatient procedure for exploration of tubo-ovarian structures and tubal patency in subfertile patients. At present, there are no large studies that relate the findings at THL to fertility outcome. METHODS: Consecutive patients undergoing THL for subfertility between 2000 and 2004 were included in this prospective cohort study. Follow-up ended when ongoing pregnancy or tubal surgery occurred or at the day of last contact. Kaplan-Meier curves for the occurrence of intrauterine pregnancy (IUP) (spontaneous or after intrauterine insemination) were constructed for a normal THL, a THL with a one-sided tubal pathology and a THL with a two-sided tubal pathology. Fecundity rate ratios (FRRs) were calculated to express the association between THL findings and the occurrence of IUP. Patients rated their pain experiences and acceptability on a visual analogue scale (VAS). RESULTS: We included 272 women. In 96% (261) of the patients, access to the pouch of Douglas was achieved. Complications occurred in 2% of the procedures. In 203 (78%) patients, both tubo-ovarian structures could be visualized and tubal patency was shown. One-sided tubal occlusion was found in 10%, whereas two-sided tubal occlusion was seen in 4% of the patients. Adhesions and/or endometriosis were observed in 8% of the patients. The FRRs for one-sided tubal pathology, two-sided tubal pathology and adhesions/endometriosis were 0.59, 0 and 0.80, respectively. The VAS scores showed pain to be limited and the procedure to be acceptable. CONCLUSION: THL is a feasible technique. Its capacity to predict spontaneous ongoing pregnancy is comparable to that of laparoscopy.

Cost-effectiveness of in vitro fertilization and embryo transfer.

OBJECTIVE: Economic analyses in reproductive medicine often fail to take into account the chances of treatment-independent conception. We compared the cost-effectiveness of several realistic strategies involving IVF using no treatment as the reference strategy. DESIGN: A decision tree was constructed for a subfertile couple in which the clinician had to decide whether to offer treatment with IVF. No treatment at all was used as the reference strategy. SETTING: An analytic decision-making framework. PATIENT(S): Hypothetical subfertile couples. INTERVENTION(S): Two potential treatment approaches: three IVF cycles performed as soon as possible, or no treatment performed initially and then three or four IVF cycles performed if a pregnancy resulting in a live birth does not occur naturally after 212 years. MAIN OUTCOME MEASURE(S): The cost of establishing one pregnancy that results in a live birth. RESULT(S): The cost-effectiveness of IVF depended not only on the costs and expected success rates of IVF itself but also on the couple-specific chances of treatment-independent conception. Consequently, the cost-effectiveness of IVF is strongly dependent on the age of the female partner. This finding corresponds with everyday clinical experience. CONCLUSION(S): Economic analyses in reproductive medicine should take into account the option of providing no treatment.

How concordant are the estimated rates of natural conception and in-vitro fertilization/embryo transfer success?

Knowledge of the chance to conceive for the subfertile couple is important in the process of counselling and clinical decision making. There are no data available on the reproducibility of the clinician's ability to assess the chance to conceive, both after expectant management or treatment with in-vitro fertilization and embryo transfer (IVF-embryo transfer). We evaluated this reproducibility by means of a set of case histories presented to a panel of gynaecologists and endocrinologists. A poor reproducibility would indicate a strong need for the use of prognostic models. In 1995, 57 gynaecologists and 32 reproductive endocrinologists were asked to appraise the 1 year spontaneous conception chance as well as the cumulative success rate of three cycles for IVF-embryo transfer of four couples with different medical histories. The clinical and laboratory data of these couples were presented as case histories. The difference between the estimated spontaneous pregnancy chances and the success rate of IVF-embryo transfer was also calculated. Calculation of intra-class correlation coefficients, which can be considered as measures of the reproducibility, demonstrated a substantial reproducibility of the assessment of spontaneous conception chances, but a slight to fair reproducibility of the assessment of IVF-embryo transfer success rates. We conclude that the use of reliable prognostic models for IVF-embryo transfer in the management of subfertility is warranted.

The performance of CA-125 measurement in the detection of endometriosis: a meta-analysis.

OBJECTIVE: To assess the diagnostic performance of serum CA-125 measurement in the detection of endometriosis. DESIGN: Meta-analysis. SETTING AND PATIENT(S): Twenty-three studies comparing serum CA-125 levels and laparoscopically confirmed endometriosis. INTERVENTION(S): Serum CA-125 measurement and laparoscopy. MAIN OUTCOME MEASURE(S): Sensitivity and specificity of serum CA-125 measurement in the diagnosis of endometriosis with laparoscopy as the reference standard. RESULT(S): The estimated summary receiver operating characteristic curves showed that the performance of serum CA-125 measurement in the diagnosis of endometriosis grade I/IV is limited, whereas its performance in the diagnosis of endometriosis grade III/IV is better. CONCLUSION(S): Despite its limited diagnostic performance, we believe that the routine use of serum CA-125 measurement in patients with infertility might be justified. In contrast to laparoscopy, serum CA-125 measurement is an inexpensive test that is not a burden for the patient. It could identify a subgroup of patients who are more likely to benefit from early laparoscopy. Studies reporting on the mutual dependence between serum CA-125 measurement and data from the history and physical examination are needed.

The effect of hysterectomy and endometrial ablation on follicle stimulating hormone (FSH) levels up to 1 year after surgery.

OBJECTIVES: In this study the hypothesis was tested, that in premenopausal patients FSH-levels would rise after 'simple hysterectomy'. As endometrial ablation is not supposed to compromise ovarian bloodflow, there would be no such change in ablated patients. METHODS: Between January 1995 and April 1996, consecutive premenopausal patients with dysfunctional uterine bleeding who were scheduled for hysterectomy or endometrial ablation were asked to participate in the study. Bloodsamples were drawn before surgery, six weeks, six months and one year after surgery. FSH and oestradiol (E2) were assayed. In all patients data about length and weight were collected to calculate Body Mass Index (BMI). Every visit patients filled in a questionnaire, containing questions about typical climacteric complaints, combined in a five-point scale. RESULTS: Except for a significant difference in preoperative FSH-level between both groups, there were no significant differences regarding age, Body Mass Index (BMI), oestradiol (E2) or the percentage of women with vasomotor complaints. Compared to the preoperative starting level, six weeks, six months and one year after surgery a significant rise in serum FSH in the hysterectomy group, as well as in the ablation group was found. However there was no significant difference in FSH increase between both groups. One third of the patients in both groups had typical climacteric complaints as flushing and nocturnal sweating. CONCLUSIONS: Assaying serum FSH-levels before and after uterine surgery and comparing hysterectomized patients and patients after endometrial ablation, we found a significant rise in FSH-level up to one year after surgery in both groups postoperatively, indicating impaired ovarian function. There was no difference in FSH-levels between both groups. Therefore major uterine surgery (hysterectomy, ablation) may prelude an earlier onset of menopause.

Regression of endometrial thickness in combination with reduced withdrawal bleeding as a progestational effect of tibolone in postmenopausal women on oestrogen replacement therapy.

For 176 postmenopausal women on HRT with progestogen addition 'on demand' medroxyprogesterone acetate (MPA), noresthisterone and tibolone were used to protect the endometrium in 214 cases. Tibolone is a gonadomimetic steroid with combined progestogenic and estrogenic effects. In this study tibolone has been used as a progestogen. The results of these three progestogens were compared. The endometrial thickness before and after the use of progestogen was determined by vaginosonography. In 175 out of 214 cases progestogen addition during oestrogen therapy caused endometrial regression. Withdrawal bleeding was observed 166 times. If the endometrial thickness on the onset of progestogen addition was 5 mm or more, in nearly all cases withdrawal bleeding occurred when MPA or norethisterone was used. If tibolone was used, no withdrawal bleeding occurred in over half the cases studied. We report the first observation of induced endometrial regression without withdrawal bleeding.

The staging of peritoneal endometriosis by the type of active lesion in addition to the revised American Fertility Society classification.

OBJECTIVE: To evaluate changes in peritoneal endometriosis by the type of lesion in comparison with the scoring system of the revised American Fertility Society (AFS) classification. DESIGN: Prospective evaluation at laparoscopy before and 6 months after discontinuance of a 3-month medical therapy with either dydrogesterone or danazol. SETTING: A general hospital. PATIENTS: Forty cycling women with endometriosis and infertility. Fourteen patients could be fully evaluated by their revised AFS score and type of peritoneal lesion. INTERVENTIONS: Laparoscopy before and 6 months after discontinuance of medical therapy. MAIN OUTCOME MEASURE: Revised AFS score and type of peritoneal lesions. RESULTS: The revised AFS score decreased or remained unchanged in 13 of 14 patients, whereas red papular or vesicular lesions were present at both laparoscopies in 5, absent in 4, disappeared in 3, and appeared de novo in 2. A changing pattern also was seen in other types of small peritoneal lesions. CONCLUSION: In contrast with the revised AFS score, the study of the type of peritoneal lesions shows a changing pattern of activity. The significance in pathophysiological and clinical studies should be investigated further.

Cyclic changes in the concentration of glucose and fructose in human cervical mucus.

OBJECTIVE: To determine a possible cyclic change in the concentration of glucose and fructose in the aqueous phase of human cervical mucus (CM). DESIGN: Concentrations of glucose and fructose were longitudinally determined in the aqueous phase of CM of normal cycling women using enzymatic techniques, modified for small quantities. SETTING: Patients visiting a fertility clinic were selected. PATIENTS: Nine healthy women with regular menstrual cycles of 28 +/- 3 days that appeared to be ovulatory, demonstrated by sonographic follicle immaging and serum progesterone (P) measurements. INTERVENTIONS: Cervical mucus samples were longitudinally collected preovulatory, postovulatory, and premenstrual in ovulatory cycles, monitored by ultrasound and blood estradiol and P measurements. MAIN OUTCOME MEASURES: The study was designed to measure glucose and fructose longitudinally on three different points during one cycle. RESULTS: The preovulatory glucose concentrations in CM were lower than postovulatory and premenstrual. The preovulatory fructose concentrations were lower than premenstrual. The glucose concentration correlated with the blood P level. CONCLUSION: There is a consistent change in the glucose concentration measured in human CM in three phases of the menstrual cycle. The preovulatory and premenstrual fructose concentrations differ significantly. Knowledge of the carbohydrate metabolism in human cervical mucus may contribute in illuminating the possible role of the carbohydrate metabolism in sperm migration at midcycle and implantation in the luteal phase.

[Indications for an increased risk of neural tube defects in pregnancies following ovulation induction and (or) in-vitro fertilization]. / Aanwijzingen voor een verhoogde kans op defecten van de neurale buis bij zwangerschappen ontstaan na ovulatie-inductie en (of) in vitro-fertilisatie.

Several authors have reported a possible association between IVF or induction of ovulation on the one hand and the occurrence of neural tube defects on the other hand. Here a review is given of recent literature on this subject, including data available from The Netherlands. Collaborative epidemiologic studies are needed to evaluate the potential risks. In individual pregnancies prenatal examination is advised. In spontaneous abortions fetal pathological evaluation is desirable.

Analysis of the aqueous phase of human cervical mucus by reversed-phase high-performance liquid chromatography and capillary isotachophoresis.

The aqueous phase of human cervical mucus was analysed by reversed-phase high-performance liquid chromatography (HPLC) and capillary isotachophoresis (ITP). With HPLC, seventeen ultraviolet-absorbing and eight fluorescent components and with ITP five anionic and four cationic components could be determined. The sample pre-treatment consisted of a simple ultrafiltration. Ten samples from fertile women and eleven samples from infertile women were analysed. In six samples from the infertile group higher median concentrations of several components were found. This may be an indication of disturbances in the biochemical processes of the cervical mucus of woman with fertility problems.

A 15-year-old girl with an expansively growing tumour.

Often decisions have to be made in acute situations, when there is no time for discussion. The decision may have extreme consequences for the patient. The case is reported of a girl aged 15 years with an expansively growing tumour of the uterus. An intra-abdominal haemorrhage was caused by a ruptured vascular connection. The aggressive behaviour of the tumour aroused suspicion of malignancy. At emergency laparotomy the tumour was enucleated from the uterus. Uterus and adnexa were preserved. The next problem in decision-making was the doubt concerning the pathological diagnosis: benign cellular leiomyoma or low-grade leiomyosarcoma. Now, 5 years after the laparotomy, there are no signs of recurrence. The problems concerning the diagnoses of 'leiomyoma' and 'leiomyosarcoma' are briefly reviewed.

A new culdocentesis system.

A new culdocentesis system is presented, based on vacuum fixation of the posterior vaginal wall together with Douglas peritoneum in a small vacuum cup, enabling a controllable central perpendicular puncture with a special catheter-needle unit. The advantages of the new system are the creation of a relatively safe and painless access to the pouch of Douglas, less risk of contamination, the possibility of repetitive examinations, and satisfactory effectiveness in collecting peritoneal fluid. The results of 164 culdocenteses in ambulant infertility patients are reported. Application of the technique is proposed for the investigation of sperm migration in vivo, steroid analysis of peritoneal fluid, and intraperitoneal insemination.

Effects of oestriol: preliminary results on receptor kinetics in target tissues of postmenopausal women.

This in vivo investigation was done to study the effects of intravaginal oestriol (E3) administration on endometrial, myometrial and vaginal tissue of normal postmenopausal women. All women received intravaginal E3- suppositoria (containing 0.5 mg E3) once a day for 3 weeks prior to hysterectomy. The medication was continued until the day of operation. At the time of operation both uterine and vaginal tissue was obtained. The receptor content in the cytosol was measured by a multiple point-dextran -coated-charcoal assay using [3H]E2 and [3H]ORG-2058 as ligands. The receptor content in the nucleus was measured by incubating purified whole nuclei in 10 nM [3H]E2 for 18 h at 0 degrees C. We have shown that under these conditions there is a total exchange of all occupied receptors. Preliminary data on 4 patients are available. Vaginal cytology clearly showed an increase of the maturation value. Oestrogen receptor concentrations in the cytosol of all three tissues studied were lower than those obtained in untreated women, suggesting nuclear transformation of the receptor as a consequence of treatment. The nuclear E2 receptor levels cannot be compared with normal women yet. Progesterone receptors in endometrial and myometrial cytosol seemed to be higher than those in untreated women, indicating effects of the treatment. In the human, vaginal progesterone receptor cannot be used as a marker for oestrogenic stimulation because only exceptionally could their presence be detected in either treated or untreated women.

Subcellular distribution of androgens and oestrogens in target tissue.

To study the endogenous concentration of androgens and oestrogens in target tissue, three different methods have been used: (a) measurement of concentration gradient across mammary tumours, (b) long-term infusion of subphysiological amounts of labelled oestrogens and measurement of tissue-plasma gradients in human uterine tissue and (c) measurement of endogenous concentrations in mammary and uterine tissues. In addition to the tissue-plasma gradient, the subcellular distribution was also measured. An improved method is presented for processing the tissue and for the quantitative extraction of steroid hormones from cytosol and nuclear fraction. The data obtained show clearly that steroid hormones have a tissue-plasma gradient that varies from tissue to tissue and from one hormone to another. As steroid hormones exert their influence intracellularly at the site of receptor binding, our findings may have major consequences for the study of hormone-related cancers of the breast and of the uterus.