Cost of assisted reproductive technologies for a health maintenance organization.

OBJECTIVE: To calculate the cost of assisted reproductive technologies (ART) for a health maintenance organization (HMO), assess factors that contribute to the cost per delivery and to analyze how utilization rates can be controlled by the use of clinical criteria. STUDY DESIGN: Pregnancy outcome and a cost analysis of all ART cycles at an HMO in a state with mandated coverage for these procedures was performed. All patients (n = 148) undergoing ART cycles insured by the HMO performed at one in vitro fertilization (IVF) center during 1990-1995 were studied. RESULTS: ART cycle outcomes and a cost analysis, including global cycle and cancellation charges, medication costs, obstetric costs and neonatal care costs, were assessed. ART cycles (n = 375) included IVF (n = 278), gamete intrafallopian transfer (n = 46), cryopreserved embryo transfer (ET) (n = 42), zygote intrafallopian transfer/tubal embryo transfer (n = 7) and donor oocyte (n = 2). Pregnancy outcome with IVF was 18.3% deliveries per retrieval, for gamete intrafallopian transfer 27.8% deliveries per retrieval and for frozen ET 19% per procedure. Overall, 62/148 (41.9%) of the patients delivered. There were 35 singletons, 22 twin sets and 5 triplet sets. This resulted in an average cycle cost per delivery of $36,417. The mean obstetric and neonatal charges were $9,329 for a singleton delivery, $20,318 for twins and $153,335 for triplets. If these charges are expressed in terms of the number of infants born, a twin pregnancy would cost $10,159 per infant and a triplet pregnancy, $51,112. The ART cycle cost per HMO plan member was $2.49 per annum. Our IVF utilization was 295 cycles per million population. CONCLUSION: An HMO can control the cost of ART services by establishing preauthorization clinical criteria. Our utilization rates might be used as a benchmark for other insurers considering ART coverage. The cost of ART ($2.49 per annum) would be only a small fraction of the typical annual insurance premium.

The sperm stress test: a novel test that predicts pregnancy in assisted reproductive technologies.

OBJECTIVE: To develop a reliable sperm test that would predict pregnancy rate in assisted reproductive technologies. DESIGN: Blind prospective cohort study. SETTING: Tertiary-care, university hospital-affiliated IVF program. PATIENTS: One hundred nineteen sperm samples were obtained from 110 males from couples undergoing IVF or GIFT (ART). Sperm samples were washed by Percoll, incubated at 24 degrees C for 4 hours, and an aliquot of the same sperm suspension was used for ART incubated at 40 degrees C for 4 hours (stress test). Stress test scores are expressed as the ratio of final to initial motility. RESULTS: Of 119 ART cycles, 24 resulted in pregnancy. Of 24 pregnancies, 23 occurred in cycles that used sperm samples with stress test scores > or = 0.75 and only one with a stress test score < 0.75. The negative predictive value of the test, defined as the absence of pregnancy with scores < 0.75, was 98% and the positive predictive value, defined as the occurrence of pregnancy with scores > or = 0.75, was 36%. Logistic regression analysis indicated that the stress test score alone was correlated significantly with pregnancy after ART. CONCLUSION: These results indicate that stress test scores < 0.75 are predictive of poor pregnancy outcome in ART.

Success rates with gamete intrafallopian transfer and in vitro fertilization in women of advanced maternal age.

OBJECTIVE: To evaluate the effect of maternal age on outcomes for IVF and GIFT in women 40 to 45 years of age. DESIGN: Retrospective. SETTING: Boston IVF, a free-standing university-affiliated IVF and GIFT unit. PATIENTS: A total of 2,931 cycles of IVF and 1,826 cycles of GIFT were analyzed in women undergoing assisted reproductive technologies (IVF or GIFT) using autologous eggs. INTERVENTIONS: Medical records of patient outcomes were reviewed. RESULTS: For patients undergoing IVF, the cancellation rate for initiated cycles showed significant differences in women aged 25 to 39 (38.3%), women aged 40 to 43 (49.5%), and women aged 44 to 45 years (69.5%). A significantly lower delivery rate per stimulation and delivery rate per retrieval was found in women aged 40 to 43 years when compared with women aged 25 to 39 years. No deliveries occurred in 59 cycles in women aged 44 to 45 years, thereby representing a significant difference when compared with both women aged 25 to 39 years and women aged 40 to 43 years. For patients undergoing GIFT, the cancellation rate for initiated cycles was significantly higher in women aged 40 to 43 (25.0%) and 44 to 45 years (31.0%) when compared with women aged 25 to 39 years (15.1%). A significantly lower delivery rate per stimulation and delivery rate per retrieval was found in women aged 40 to 43 and 44 to 45 years when compared with women aged 25 to 39 years. CONCLUSIONS: Success rates for IVF and GIFT decline significantly in women > 40 years old. Women aged > or = 44 years are unlikely to benefit from the use of IVF and GIFT.

Comparison of unilateral and bilateral tubal transfer in gamete intrafallopian transfer (GIFT).

Gamete intrafallopian transfer (GIFT) is traditionally performed by delivering gametes into the ampullary region of either one or two fallopian tubes. The choice is made by the surgeon at the time of laparoscopy based upon the patient's anatomy, the number of oocytes available, and clinical judgment. In this nonrandomized, retrospective review, 399 tubal gamete transfers were performed over a period of 18 months, 133 to a single tube and 266 to both tubes. A clinical pregnancy rate of approximately 24% was observed in each modality. The multiple pregnancy rate of 31.3% for one tube was not significantly different from the 25% seen for two tubes. Unilateral tubal transfer offers the distinct advantages of less gamete and tissue handling. This, along with the apparent same outcome parameters, makes unilateral tubal transfer the preferred method of returning gametes at GIFT.

Gamete intrafallopian transfer: assessment of the optimal number of oocytes to transfer.

The optimum number of oocytes that should be transferred at the time of gamete intrafallopian transfer (GIFT) is important information. Nonessential oocytes can be inseminated and frozen for later use or the extra oocytes can be donated to another women. In this preliminary study, the results of 399 consecutive GIFT procedures were evaluated retrospectively as a function of the number of oocytes transferred. Women who received four or more oocytes were three times more likely to achieve a clinical pregnancy than those who received three or less. There was no statistically significant difference in pregnancy rates between patients who received five, six, seven, or eight oocytes. Oocytes in excess of five may be more effectively used if they are fertilized and frozen as embryos for later transfer rather than replacing them all at the time of GIFT.

Successful use of gamete intrafallopian transfer does not reverse the decline in fertility in women over 40 years of age.

To assess the impact of assisted reproductive technologies on the potential fertility of older women, we report our experience with gamete intrafallopian transfer (GIFT) in a large number of women 40 years of age and older. One hundred twenty-two GIFT cycles were initiated in 59 women over 18 months. Seventy-three tubal transfers were performed, resulting in seven clinical pregnancies, a rate of 9.6% per transfer. This contrasts with a 27.3% clinical pregnancy rate per transfer in women under 40. Thus, older patients require thorough counseling regarding the decreased likelihood of success despite the use of assisted reproductive technologies.

Pregnancy after gamete intrafallopian transfer in a woman with primary infertility and in utero exposure to diethylstilbestrol. A case report.

In utero exposure to diethylstilbestrol (DES) has an adverse effect on reproductive performance and may be associated with infertility. Gamete intrafallopian transfer (GIFT) is a new reproductive technique that has been advocated as an alternative to in vitro fertilization in women with at least one normally functioning fallopian tube. The process involves the translaparoscopic placement of oocytes and sperm into the fallopian tube. The technique has been successful in treating infertility due to endometriosis, male factors and immunologic factors as well as unexplained infertility. We accomplished the first successful GIFT procedure in a woman with significant uterine effects from prenatal DES exposure. This technique may prove to be an effective treatment for infertile women with DES exposure who have no adequate explanation for their infertility.

Fundamental ethical principles in health care.

KIE: In an attempt to clarify which requirements of morality are logically primary to the ethics of health care, two questions are examined: is there sufficient common ground among the medical, nursing, paramedical, chaplaincy, and social work professions to justify looking for ethical principles common to health care? Do sufficient logical grounds or consensus among health workers and the public exist to speak of "fundamental ethical principles in health care"? While respect for persons, justice, and beneficence are fundamental principles in a formal sense, how we view these principles in practice will depend on our particular culture and experience and the kinds of metaethical criteria we use for applying these principles.^ieng

Disappearance of human chorionic gonadotropin following removal of ectopic pregnancy.

A study was undertaken to determine the length of time serum beta-subunit of human chorionic gonadotropin (beta-hCG) could be detected following removal of ectopic pregnancy. Seven patients underwent complete removal of trophoblastic tissue by either salpingectomy or partial resection of the involved fallopian tube. Nine other patients had conservative surgical treatment by either linear salpingostomy or fimbrial expression of the fallopian tube. Serum beta-hCG levels were determined serially in all these patients. The results demonstrate that the initial titer of hCG is a significant factor in determining the length of time that it can be detected in the serum postoperatively. In addition, decreasing titers, conforming to the disappearance curve of hCG, as constructed in this study, are a helpful aid in avoiding further surgery in the group of patients who had a conservative removal of the trophoblastic tissue. Finally, the serum clearance of hCG by radioimmunoassay may take at least up to 24 days after surgery.

Urinary estrogen and serum gonadotropin profiles in women ingesting oral contraceptive steroid formulations with variable estrogen content.

PIP: Urinary estrogen and serum gonadotropin were measured via fluorometric and radioimmunoassay techniques in 14 presumptively ovulatory women ingesting contraceptives of variable estrogen content. Blood and urine samples were collected on days 6-8, 12-17, and 22-24 of control and therapeutic cycles, and data were used to calculate mean hormone levels for respective cycle phases. Contraceptive formulations contained 1 mg norethindrone acetate and either 20 mcg or 50 mcg ethinyl estradiol. Consistently higher estrogen levels and higher luteinizing hormone levels were found in women ingesting norethindrone acetate 1 mg plus 20 mcg ethinyl estradiol. These differences were statistically significant and were consistently more pronounced during the early phase of therapeutic cycles. These findings may reflect possibly enhanced luteinizing-hormone-mediated ovarian steroidogenesis in the absence of apparent ovulation.^ieng

The role of ultrasound in ovulation induction: a critical appraisal.

Twenty-five cycles induced by human menopausal gonadotropin (hMG) were serially studied by ultrasound. The developing follicles were observed up to and beyond human chorionic gonadotropin (hCG) administration. Ovulation as determined by subsequent pregnancy or a sustained elevation of basal temperature was seen in 18 of these cycles. Among these patients the follicular size ranged between 24 and 13 millimeters. No pregnancies occurred where the follicular size was below 15 mm. A shortened luteal phase was noted in three cycles where the follicular size was either 13 or 14 mm. Multiple follicles greater than 10 mm were observed in 14 of the ovulating cycles, but in no case did a multiple pregnancy occur. Fifteen millimeters is therefore suggested as a minimum size for satisfactory ovulation, but it does not appear that an optimum size exists. We conclude that ultrasound can play an important role in the monitoring of ovulation induction but does not replace the present methods.

Learning about death: a project report from the Edinburgh University Medical School.

A report of a problem-based learning project on the ethics of terminal care, offered as one of the options available to first year MB ChB students in Edinburgh University Medical School. The project formed part of the 'clinical correlation course' in the new curriculum. Six students took part under the supervision of two clinical tutors and a moral philosopher. The course was case-based and practical with students being given the opportunity over a period of eight weeks to meet patients, relatives and hospital staff at a local geriatrics hospital and terminal care home. The main issue studied was the degree of choice available to patients electing to be treated at home, in hospital or in a hospice. Other issues included: pre-death, disposal of the dead, certification of death, communication with relatives and follow-up bereavement services.

Research ethical committees in Scotland.

A questionnaire was sent to 41 ethical committees in Scotland requesting information about their constitution and supervision of clinical research. Thirty-four (83%) replies were received. Committees varied in size from one to 73 members, most of whom were medical. Ten had no nurse members and only three had lay members without direct NHS connections. Sixteen saw their role as advisory rather than supervisory. Thirteen had not met in the past year whereas two had held 10 or more meetings. Limited use (12) was made of standard protocols, and only six had formal procedures for monitoring research in progress. Only seven of 370 proposals were rejected outright. Risk/benefit dilemmas and difficulties relating to informed consent were the commonest problems encountered. The committees provide only limited safeguards for patients and research workers, and more effective, standardised procedures are indicated.

Luteal phase deficiency and infertility: difficulties encountered in diagnosis and treatment.

Uncertainty concerning the importance of luteal phase defects as a cause of female infertility is closely related to problems of diagnosis. A study was undertaken of the consistency of the parameters used in daignosing luteal phase deficiency in 14 patients; results of randomized treatment regimens were also compared. Specific diagnostic criteria utilizing the basal body temperature (BBT) chart, endometrial biopsy, and progesterone levels were used. Prolactin and luteinizing hormone levels were measured at the time of progesterone determinations. Of the 29 cycles studied, only one third showed consistent abnormalities in BBT chart, endometrial biopsy, and progesterone levels. Discrepancy between the endometrial biopsy and the progesterone level occurred in at least 50% of all cycles studied. Prolactin levels were elevated in only 1 patient, suggesting a minor role for altered prolactin metabolism in luteal phase deficiency. Randomized treatment with progesterone vaginal suppositories, clomiphene citrate, and no treatment resulted in pregnancy in 5 of 14 patients (36%).

The nature of confidentiality.

This paper examines confidentiality and its nature and analyses the guidelines laid down by the Hippocratic Oath as well as the British and World Medical Associations for maintaining such confidentiality between doctor and patient. There are exceptions to practically any code of rules and this is true also for confidentiality. Some of these exceptions make it appear that very little is confidential. The three values implicit in confidentiality would seem to be privacy, confidence and secrecy. Each of these values is discussed and developed in this paper. In conclusion, the question is suggested that maybe in the face of death, doctor and patient need to re-examine the pre-suppositions of privacy, confidence and secrecy on which the confidential relationship is based.

Diagnostic value of androgen measurements in polycystic ovary syndrome.

A group of 51 women with a diagnosis of polycystic ovary syndrome (PCO) were investigated. They were further classified into PCO Type I and PCO Type II based on clinical and laboratory investigations. Serum levels of unbound (free) and total testosterone, testosterone binding globulin (TBG), and androstenedione were measured in these women and compared with values in normal women. Mean levels of all these steroids were elevated in women with PCO. No difference in adrogen levels was found between women with PCO Type I and PCO Type II. Serum unbound testosterone concentrations correlated better with the presence and severity of hirsutism than did the total testosterone.