Guideline adherence in ectopic pregnancy management.

BACKGROUND: Evidence-based guidelines have been issued for ectopic pregnancy (EP), covering both diagnostic and therapeutic management. In general, guidelines aim to reduce practice variation and to improve quality of care. To assess the guideline adherence in the management of EP, we developed guideline-based quality indicators and measured patient care in various hospitals. METHODS: A panel of experts and clinicians developed quality indicators based on recommendations from the Dutch guideline on EP management, using the systematic RAND-modified Delphi method. With these indicators, patient care was assessed in six Dutch hospitals between January 2003 and December 2005. For each quality indicator, a ratio for guideline adherence was calculated. Overall adherence was reported, as well as adherence per hospital type, i.e. academic, teaching and non-teaching hospitals. RESULTS: Out of 30 guideline-based recommendations, 12 quality indicators were selected covering procedural, structural and outcome aspects of care. For 317 women surgically treated for EP, these aspects were assessed. Overall adherence to the guideline was 75%. The highest adherence (98%) was observed for performing transvaginal sonography during the diagnostic workup. The lowest adherence (21%) was observed for performing salpingotomy in case of contra-lateral tubal pathology. Wide variance in adherence (0-100%) existed between academic, teaching and non-teaching hospitals. CONCLUSIONS: The overall guideline adherence was reasonable, with ample room for improvement in various aspects of care. Further research should focus on the barriers for guideline dissemination and adherence, to further improve the management of EP.

Is there a carryover effect of mild ovarian hyperstimulation with gonadotropins on the subsequent cycle?

OBJECTIVE: To investigate the effect of mild ovarian hyperstimulation on hormonal and sonographic variables of the subsequent natural cycle. DESIGN: Prospective study of three consecutive cycles. SETTING: University Hospital, Department of Reproductive Medicine, Division of Obstetrics and Gynecology. PATIENTS: Twelve couples with subnormal semen as the only identifiable cause of subfertility. INTERVENTIONS: Subjects were offered IUI for three cycles. In the second cycle, mild ovarian hyperstimulation with 75 IU IM hMG was applied daily and ovulation was induced with 5,000 IU hCG. In the first and third both natural cycles, serum samples were obtained for hormone measurements and ultrasound (US) scanning of the ovaries was performed. MAIN OUTCOME MEASURE: To determine whether there was a carryover effect of mild ovarian hyperstimulation as applied in the second cycle, hormone levels and US scans of cycle 3 were compared with those of cycle 1. RESULTS: None of the variables of cycle 3 were significantly different from those of cycle 1. CONCLUSION: Because hormonal and sonographic variables in the subsequent natural cycle remain unchanged, a carryover effect of mild ovarian hyperstimulation with gonadotropins seems unlikely.

The pattern of the luteinizing hormone surge in spontaneous cycles is related to the probability of conception.

OBJECTIVE: To determine whether the pattern of the LH surge in a treatment cycle with artificial insemination with the husband's semen (AIH) because of cervical factor infertility is associated with the probability of conception. DESIGN: Retrospective study. SETTING: University Hospital, Department of Obstetrics and Gynecology. PATIENTS: Couples with cervical factor infertility as the main cause of subfertility. INTERVENTIONS: Luteinizing hormone monitored AIH. MAIN OUTCOME MEASURE: Whether or not a pregnancy occurred after AIH. RESULTS: There were 53 pregnancies in 382 IUI cycles (pregnancy rate [PR] per cycle: 13.9%). The PR was significantly higher in cycles with an LH surge of 2 days compared with cycles with a surge of 1 day. The probability of conception also seemed to be related to the height of the LH surge. CONCLUSION: The pattern of the LH surge in patients with cervical factor infertility is related to the outcome of a treatment with AIH.

Low luteal phase serum progesterone levels in regularly cycling women are predictive of subtle ovulation disorders.

Serial hormonal and ultrasound measurements were performed in a group of 50 infertile women with regular menstrual cycles of normal length, and evidence of luteinization by measurement of biphasic basal body temperature (BBT). The progesterone levels however, remained below a critical threshold of 32 nmol/l (1 nmol/l = 0.315 ng/ml) in two cycles. In 50 cycles, 25 showed definite abnormalities. In 16 other cycles, ovulation was observed, but relatively low luteal progesterone followed. Although pregnancy in these 16 cycles could be less likely, the real significance of this finding is questionable. The etiology of these 'subtle cycle anomalies' is not clear and may be multifactorial. For this reason, no therapy other than use of ovulation-inducing agents by trial and error is as yet available. Preliminary results indicate that cycle disturbances may persist under ovulation induction, even though progesterone levels are normalized.

Diagnosis of subtle ovulation disorders in subfertile women with regular menstrual cycles: cost-effective clinical practice?

Serial monitoring by plasma progesterone measurement is advised in the literature for fertility work-up, to detect ovulation disturbances in women presenting with regular menstrual cycles. Three strategies to diagnose such 'subtle ovulation disorders' (SOD, defined as anovulation, inadequately timed ovulation or ovulation of a follicle of reduced size in regularly cycling women) were evaluated, in order to investigate costs of such a diagnosis. On the basis of a 'maximal', an 'ultrasound-only', and a 'preselection' strategy, total medical costs and costs including non-medical costs were calculated for each SOD diagnosis. A 'maximal' diagnostic strategy resulted in a total medical cost of ECU 9057 per diagnosis (including non-medical costs ECU 12,787); an 'ultrasound-only' strategy in ECU 4520 (ECU 6791) per diagnosis. By use of a 'preselection' strategy, 4.25% of the women were found to have an SOD, at a cost of ECU 3036 (ECU 6868) for each diagnosis. As the real significance of SOD diagnosis for the prognosis of the patient to become pregnant without treatment remains unclear, and as no randomized trials on treatment effectiveness have as yet been undertaken, it is questionable whether this approach is worthwhile.

Hormone patterns after induction of ovulation with clomiphene citrate: an age-related phenomenon.

Since the introduction of clomiphene citrate (CC), more than three decades ago, a discrepancy has been observed between ovulation and pregnancy rates for which as yet no explanation exists. To investigate if ovulation disorders or abnormal hormonal patterns occur more often in CC-stimulated seemingly ovulatory cycles, we performed hormonal and sonographic monitoring in first cycles of oligo- or amenorrheic patients who were stimulated with 50 mg CC, and compared the hormonal patterns to those in natural cycles of age-matched proven fertile women. Twenty-four first CC cycles were monitored. Twelve cycles appeared to be ovulatory, eleven showed no follicle development and one cycle exhibited the luteinized unruptured follicle (LUF) phenomenon. Ten ovulatory cycles were compared with 27 unstimulated control cycles. In four cycles stimulated by CC, a temporary decline in estradiol levels was apparent. In these cycles, estradiol reached a higher level on cycle day (CD) 7 or 8 compared to cycles without a decline. Such an estradiol decline was seen in only one control cycle. Furthermore, the estradiol levels on CD 7 or 8 appeared to be age-related. We conclude that the estradiol decline in CC-stimulated ovulatory cycles may be a consequence of a sharp rise after CC stimulation, and such a rise may be age-related and coincide with a diminished follicle quality. If this phenomenon is associated with a suboptimal cycle, and so contributes to the suboptimal pregnancy rates after ovulation-induction treatment with clomiphene citrate, is still unknown.

A patient with a progesterone-producing adrenal adenoma who presented with primary amenorrhea.

A case report is presented of a patient with a primary amenorrhea due to a progesterone-producing adrenocortical adenoma. Clinical and endocrinological abnormalities disappeared after removal of the tumor, and the patient experienced her menarche. To our knowledge, a predominantly progesterone-producing adrenal adenoma--in this patient associated with the clinical picture of primary amenorrhea--has not previously been described.

Intra-uterine insemination or timed intercourse after ovarian stimulation for male subfertility? A controlled study.

In this randomized trial we investigated whether intra-uterine insemination (IUI) in couples with male subfertility leads to a higher probability of conception than timed intercourse after ovarian stimulation with human menopausal gonadotrophin (HMG) and human chorionic gonadotrophin (HCG). A total of 76 couples started 249 cycles, of which 47 were cancelled to prevent multiple pregnancies or hyperstimulation. After 202 completed treatment cycles, 15 pregnancies occurred, 11 after IUI and four after timed intercourse. The pregnancy rate per completed cycle with IUI was 10.3% (95% confidence interval: 5.5-17.5%) and 4.2% (1.2-10.1%) with timed intercourse. Compared with the estimated spontaneous chance to conceive, IUI after ovarian stimulation appeared to be more effective in the first three cycles. We conclude that in subfertile couples with a male factor, IUI tends to improve the probability of conception as compared to timed intercourse when ovarian stimulation is applied, and we advise such treatment for three cycles.

Familial idiopathic premature ovarian failure: an overrated and underestimated genetic disease?

The incidence of familial cases of premature ovarian failure varies from 4 to 31%. Recall bias may explain part of the variance. Thorough evaluation of alleged affected relatives showed a lower incidence than the original family history suggested. In the present study the incidence of familial cases was 12.7%. Pedigree studies on affected families showed a mode of inheritance suggestive of autosomal dominant sex-limited transmission or X-linked inheritance with incomplete penetrance. An adequate family history can distinguish between familial or sporadic premature ovarian failure. The risk of female relatives developing premature ovarian failure may be as high as 100% in familial premature ovarian failure, or as low as 1% in sporadic cases.

Do cycle disturbances explain the age-related decline of female fertility? Cycle characteristics of women aged over 40 years compared with a reference population of young women.

BACKGROUND: The cause of declining fertility with age, in women who still have regular menstrual cycles, is not clear. METHODS: Follicle development, endometrial growth and hormonal patterns were evaluated in cycles of older women (aged 41-46 years; n = 26) who previously were normally fertile, and these cycles were compared with a reference group of relatively young fertile women (aged 22-34 years; n = 35). RESULTS: Clearly abnormal cycles were found in only two women in the older age group, and in one woman in the younger group. The main differences between the age groups were a shorter follicular phase and cycle length in the older group, in combination with higher FSH levels in the late luteal and early follicular phase. In contrast to published data which suggest an "accelerated" follicle development in older women, sonographical and hormonal evidence was found of an "advanced" follicle growth, with an earlier start already during the luteal phase of the preceding cycle, and an advanced selection and ovulation of the dominant follicle. CONCLUSIONS: Such an earlier start of follicle growth in a possibly less favourable hormonal environment, as well as a limited oocyte pool, may contribute to a decreased follicle and oocyte quality, resulting in diminished fertility in ageing women.