Embryo donation: outcome and attitudes among embryo donors and recipients.

The outcome of an embryo donation programme was evaluated and attitudes among donors and recipients studied by means of a questionnaire survey. A total of 27 couples went through 54 treatment cycles with frozen-thawed embryos donated by other infertile couples. The indications for treatment were premature or incipient ovarian failure in combination with severe male factor infertility. The mean age of the recipient women was 36 years, and that of the recipient men was 35 years. The mean duration of infertility was 8 years (range 2-19 years). Forty-six couples donated 209 excess frozen embryos to the programme. The clinical pregnancy rate in the recipients was 27.8% (15/54) per embryo transfer. An average of 1.9 embryos were transferred on each occasion. The response rate to the questionnaire was high (80-91%). Significantly more recipients (69%) than donors (47%) considered that the child should be informed about the manner of conception (P < 0.05). Some 29% of recipients and 42% of donors thought that the child should receive identifying information concerning the donor couple. The interest of the offspring, not only as regards knowing his/her genetic origin but also knowing full-blood genetic siblings, should be kept in mind in embryo donation programmes.

The decrease in luteinizing hormone secretion in response to weight reduction is inversely related to the severity of insulin resistance in overweight women.

Controversial effects of weight reduction on gonadotropin secretion in obesity have been reported. As a result of pulsatility, single serum samples or frequent sampling studies are somewhat limited with regard to monitoring LH and FSH concentrations. We studied follicular phase nocturnal urinary (nu) LH and FSH secretion and glucose metabolism (150-min euglycemic hyperinsulinemic clamp) during 1 menstrual cycle/30-day period before and after weight reduction in 10 severely overweight infertility patients (age, 29 +/- 3.1 yr; body mass index, 37.1 +/- 3.3 kg/m2; +/-SEM). A 6-week very low calorie diet was followed by a 4-week normocaloric period. The urinary LH and FSH results reported represent samples taken 12 to 2 days before the LH surge, or 10 consecutive samples in the case of amenorrhea. We observed a decrease of 8% (P < 0.001) in percent body fat mass and a 5% (P < 0.005) reduction in waist to hip ratio. Mean nu-LH decreased by 45% [6.06 +/- 1.05 (+/-SEM) to 3.22 +/- 0.71 IU/L], whereas mean nu-FSH remained unchanged. Insulin-stimulated glucose uptake increased by 41% (P < 0.01), which was accounted for by a significant increase in nonoxidative glucose disposal (P = 0.003). Serum sex hormone-binding globulin concentrations increased by 39% (P < 0.01), and insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) levels increased by 46% (P < 0.05). Fasting serum insulin concentrations decreased by 38%, those of leptin by 37%, those of androstenedione by 32%, those of testosterone by 20% (all P < 0.01), and those of dehydroepiandrosterone sulfate by 13% (P < 0.05). The percent change in nu-LH correlated negatively with glucose uptake (r = -0.76; P < 0.01) and the increase in serum sex hormone-binding globulin (r = -0.85; P < 0.005) and positively with the percent change in waist to hip ratio (r = 0.79; P < 0.01). The absolute nu-LH levels after weight reduction correlated significantly with fasting insulin concentrations (r = 0.88; P < 0.001) and negatively with glucose uptake (r = -0.67; P < 0.05). No significant relationships were found between absolute levels or changes in nu-LH concentrations and leptin, IGF-I, IGFBP-3, or IGFBP-1 concentrations. Our findings suggest that weight reduction with a very low calorie diet results in a decrease in nu-LH concentrations, a reduction in the LH/FSH ratio, and FSH predominance favoring folliculogenesis. The decrease in LH concentrations is inversely related to the severity of insulin resistance. It is possible that the decrease in LH secretion with weight reduction is more dependent on the absolute levels of insulin sensitivity than on the degree of general adiposity.

Comparison of two recombinant follicle-stimulating hormone preparations in in-vitro fertilization: a randomized clinical study.

A randomized comparison of two recombinant human follicle-stimulating hormone (recFSH) preparations (Gonal-F and Puregon) in ovarian stimulation for in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) was carried out at the Infertility Clinic of the Family Federation of Finland. A total of 348 women (aged 22-43 years) suffering from infertility due to miscellaneous causes was recruited. Of these, 344 underwent stimulation using equal starting doses (150 IU/day: Gonal-F n = 164, Puregon n = 158 or 300 IU/day: Gonal-F n = 8, Puregon n = 14) after down-regulation with intranasal buserelin from the mid-luteal phase. Similar clinical pregnancy rates were achieved with both preparations; 33.5% per cycle and 37.4% per embryo transfer (24.5% one-embryo and 75.5% two-embryo transfers, n = 147) with Gonal-F (150 IU/day) and 32.9% per cycle and 36.4% per embryo transfer (30.1% one-embryo and 69.9% two-embryo transfers, n = 145) with Puregon (150 IU/day). The ongoing cumulative pregnancy rates after frozen-thawed embryo transfer were 35.4% with Gonal-F and 37.7% with Puregon. Six cycles were cancelled because of a low response (three in each group). Similar numbers of oocytes were obtained in both groups; 13.0 with 150 IU/day and 6.1 with 300 IU/day Gonal-F, and 12.4 with 150 IU/day and 7.1 with 300 IU/day Puregon. The fertilization and cleavage rates and the incidence of moderate or severe ovarian hyperstimulation syndrome (Gonal-F, 2.0% and Puregon, 0.7%) were also similar. Gonal-F and Puregon were equally and highly effective in stimulation for IVF and ICSI.

Serum and follicular fluid leptin during in vitro fertilization: relationship among leptin increase, body fat mass, and reduced ovarian response.

The satiety factor leptin is expressed in several reproductive tissues, but its role in the control of reproductive physiology is not well understood. We studied leptin concentrations in the sera and follicle fluids of 52 women [body fat mass percentage (BFM%) range, 19.6-38.8%] undergoing pituitary down-regulation and ovarian hyperstimulation for in vitro fertilization (IVF) treatment. Fasting serum samples were collected 1) at maximal suppression before the initiation of gonadotropin treatment, 2) at maximal ovarian hyperstimulation, 3) at the time of oocyte retrieval, and 4) 16 days later when all subjects were under exogenous luteal support using 600 mg progesterone daily. Follicular fluid (FF) was obtained at oocyte retrieval from two representative preovulatory follicles in both ovaries. During ovarian hyperstimulation there was a significant 60% increase in serum leptin concentrations from 10.9 +/- 1.1 (SEM) to 15.7 +/- 1.5 ng/mL (P < 0.01) between suppression and maximal hyperstimulation, demonstrating that the ovarian functional state can affect serum leptin concentrations. A serum leptin increase of 22-198% during ovarian hyperstimulation was evident in 43 subjects, whereas in 9, leptin concentrations remained unchanged. A positive correlation between leptin change and BFM% (r = 0.55; P < 0.0005) was observed in the 43 leptin responders. The follicular fluid leptin level was similar to that in serum. In separate linear regression analysis, BFM% contributed to 59-64%, body mass index to 46-56%, and weight to 46-55% (all P < 0.001) of the variability in leptin concentrations at the 4 time points. The 20-fold increase in serum estradiol concentrations during IVF was not significantly correlated with changes in leptin concentrations. On the contrary, the relative serum leptin increase was negatively associated with the ovarian response to hyperstimulation, as revealed by the numbers of follicles (b = -0.28; r2 = 8.1%; P < 0.05) and oocytes retrieved (b = -0.39; r2 = 15.2%; P < 0.01). This relationship was further reflected in a positive correlation between the percent increases in leptin and FSH concentrations (r = 0.39; P < 0.01). The significant relationship of high leptin and reduced ovarian response was also maintained when the cumulative dose of FSH was used as a covariable. Reduced ovarian response was not a function of body mass index, BFM%, basal leptin levels, or insulin concentrations. Fasting serum insulin concentrations remained unchanged in response to IVF, but were positively correlated to serum leptin concentrations at all four time points. Our data suggest that leptin production may be influenced by the ovarian functional state. During IVF a high relative leptin increase is associated with adiposity and a reduced ovarian response. These observations support the possibility that high leptin concentrations might reduce ovarian responsiveness to gonadotropins. Hence, leptin might explain in part why obese individuals require higher amounts of gonadotropins than lean subjects to achieve ovarian hyperstimulation.

Pregnancy resulting from intracytoplasmic injection of spermatozoa from a frozen-thawed testicular biopsy specimen.

A testicular biopsy specimen was taken in connection with scrotal exploration of a healthy 35 year old man who had azoospermia. Bilateral severe scarring of unknown aetiology was found in the exploration, and no epididymal spermatozoa could be obtained. Spermatozoa from the fresh biopsy specimen were used for intracytoplasmic sperm injection (ICSI) on the same day. Two-embryo transfer resulted in biochemical pregnancy. The rest of the biopsy specimen was frozen as small pieces of tissue using glycerol as a cryoprotectant. ICSI was then performed with spermatozoa prepared from the frozen-thawed tissue. One embryo was obtained and transferred. The transfer resulted in pregnancy, and a living fetus was seen in ultrasound scans at the seventh and 16th weeks of pregnancy. It is possible to avoid repeated testicular biopsies by using cryopreservation of testicular tissue.

The influence of sperm morphology and the number of motile sperm inseminated on the outcome of intrauterine insemination combined with mild ovarian stimulation.

OBJECTIVE: To determine the influence of sperm morphology and the number of motile sperm inseminated on the outcome of IUI in hMG-stimulated cycles and to establish lower limits for these variables below which the expectation of pregnancy is limited. DESIGN: Retrospective study of data from 1990 to 1992. SETTING: Tertiary referral Reproductive Medicine Unit. PATIENTS: Couples with bilaterally patent fallopian tubes, and > or = 200,000 motile sperm recovered in a trial preparation before treatment. No other semen criteria were used to exclude couples. Women were stimulated with hMG irrespective of whether they were ovulatory or anovulatory. The study comprised 163 couples who underwent 330 cycles. MAIN OUTCOME MEASURES: Pregnancy rate (PR) per cycle was related to the percentage normal sperm morphology in the fresh semen sample and the number of motile sperm inseminated after sperm preparation by swim-up or Percoll gradients. RESULTS: The overall PR was 16.1% per cycle. The PR was highest in the first cycle of treatment (21.4%) and declined in the second and third cycles. The miscarriage rate was 10.4% and the incidence of multiple pregnancies was 13.9%. Two groups of patients were defined on the basis of sperm morphology: a "poor outcome" group ( < or = 10% normal) and a "good outcome" group ( > 10% normal). The PRs in these two groups were 4.3% and 18.2%, respectively, and the cumulative PRs after three cycles were 8.3% and 40.1%, respectively. The number of motile sperm inseminated did not significantly affect the PR. CONCLUSIONS: The degree of teratozoospermia affected the PR in hMG-stimulated IUI cycles and a normal morphology value of 10% in the fresh semen distinguished couples with good and poor outcomes. In contrast, the number of motile sperm inseminated did not significantly influence IUI outcome.

Half-life of the maternal IgG1 allotype in infants.

The residence time of maternal IgG1 in the circulation of infants was measured by monitoring f-allotypic IgG1 or f-positive tetanus toxoid antibody in genetically G1mf-negative infants. G1ma-positive maternal tetanus toxoid antibody was similarly monitored in genetically a-negative infants. Blood samples were taken from infants at the age of 1-3 days, ca. 4 months, and ca. 6 months. An exponential decay at the same rate took place from age 1-3 days to 4 months and for the 2 subsequent months. The average concentration of the maternal IgG1 had dropped to ca. 10% of the 1- to 3-day value in 4 months and to ca. 3% in 6 months. The drop was due mainly to clearance but partly also to the weight increase of the child (doubling in 6 months). By correcting for the weight increase, we calculated that ca. 17 and 7% of the original maternal IgG1 was still present at ages 4 and 6 months, respectively. The average half-life of the maternal IgG1 was thus 48.4 days. The concentration of endogenous IgG1 in the cord blood was determined by studying a separate series of mother-newborn pairs. Assuming that cross-reactions of antiallotype reagents had no effect, the highest measured concentration of f-positive IgG1 in infants of f-negative mothers was 10 mg/L, half a percent of adult heterozygote values. Crossreaction may have played a role, however, and the value must be considered the upper limit of the true concentration.

Mass screening for endometrial cancer directed in risk groups of patients with diabetes and patients with hypertension.

BACKGROUND: The interest in mass screening programs for the early detection of endometrial cancer (EC) has grown with the rising incidence of this disease. Preliminary programs directed at asymptomatic women with only one risk factor, i.e. age, have not been cost-effective. METHODS: In the current study, 597 asymptomatic women from 45-69 years of age with diabetes and/or hypertension were screened by Vabra (Berkeley Medevices Inc., Berkeley, CA) aspiration. RESULTS: Among the women with diabetes, 6.3% preinvasive lesions of the endometrium were found. This is significantly more than the rate among women with hypertension, which was 1.3% (P < 0.01). CONCLUSIONS: Regular mass screening programs for the early detection of EC should be directed at asymptomatic diabetic women 45 years of age or older. This study does not indicate that similar screenings would be effective for women with hypertension.

[Hormone treatment in the climacteric]. / Hormonbehandling i klimakteriet.

To improve the quality of life among women during the three decades following the menopause, every effort should be made to prevent the adverse effects of ageing. Broad joint initiatives, involving various disciplines such as, cardiology, urology, oncology, orthopaedics and gynaecology, are needed to optimise medical care during the climacteric. Oestrogen-progesterone treatment is the most important means currently available for the prevention of postmenopausal problems. This form of hormone therapy also appears to provide protection against osteoporosis and cardiovascular disease.

Conservative treatment of ectopic pregnancy.

As a conservative nonsurgical treatment of an early ectopic pregnancy, local prostaglandin, parenteral or local methotrexate, local hyperosmolar glucose, and also expectant management have been used successfully in selected cases. The success rate of conservative treatment has been 71%-100% and that of tubal patency after different kinds of conservative treatment 72-93% of patients. In the present study of expectant management in early ectopic pregnancy in patients with decreasing serum hCG levels, spontaneous resolution was observed in 64.6% of patients and in the total series of 207 ectopic pregnancies in 15.0% of patients. Expectant management of early ectopic pregnancy is recommended when emergency surgery is not needed on admission and the serum hCG level is decreasing as noted in two consecutive estimations with an interval of 1-2 days.

Testosterone-secreting virilizing adrenal adenoma with human chorionic gonadotrophin receptors and 21-hydroxylase deficiency.

A 60-year-old woman was evaluated for persistently elevated serum testosterone concentrations after bilateral ovariectomy. Her serum cortisol, androstenedione, dehydroepiandrosterone sulphate and 17-hydroxyprogesterone levels were normal, and decreased after dexamethasone administration. Those of testosterone (17.8-18.4 nmol/l) were remarkably high (normal range 0.7-2.8 nmol/l), were not suppressed by dexamethasone, but clearly increased after hCG administration (up to 128 nmol/l). Computed tomography revealed an adenoma in the right adrenal gland and adrenal scintigraphy under dexamethasone suppression visualized this adenoma. A right adrenalectomy was performed. (1) The tumour was histologically and ultrastructurally adrenocortical adenoma of zona reticularis cell type. (2) The adenoma tissue contained hCG receptors (198 fmol/g). (3) During tissue culture both ACTH and hCG were capable of maintaining its testosterone production, which was attenuated with time without stimulation. (4) The adenoma tissue did not elaborate 21-hydroxylated steroids in contrast to normal adrenal tissue. Thus the aberrant endocrine behaviour of this gonadotrophin-responsive testosterone-secreting adenoma of adrenal zona reticularis cell origin can be explained by ectopic functional hCG receptors and the lack of 21-hydroxylase activity.

Pulsatility of serum-luteinizing hormone during hyperstimulation with clomiphene citrate and human menopausal gonadotropin for in vitro fertilization.

The pulsatile pattern of gonadotropin secretion regulates follicular growth and corpus luteum function in normal cycles, but the role of endogenous gonadotropin pulses in hyperstimulated cycles is unclear. We studied pulsatility of serum-luteinizing hormone (LH) in the late follicular and midluteal phases in four women after hyperstimulation with clomiphene citrate, human menopausal gonadotropin, and human chorionic gonadotropin, and in five women with normal untreated cycles. In the late follicular phase, the number, interval, amplitude, and area of LH pulses did not show significant differences between hyperstimulated and control cycles. In the midluteal phase, the long-lasting (greater than 90 minutes) LH pulses typical for the normal luteal phase, were not found after hyperstimulation. As the length of the luteal phase in these cases was normal, the significance of this finding remained obscure.

Ovarian stimulation during gonadotropin treatment after hCG administration monitored by ultrasound and serum estradiol and progesterone.

Ovarian volumes, measured with ultrasound, and serum estradiol and progesterone concentrations were studied during gonadotropin treatment cycles 1 week after hCG administration in 23 patients, of whom nine had polycystic ovarian syndrome (PCO), eight oligomenorrhea or amenorrhea corresponding to WHO group II (OMG), and six hypogonadotropic amenorrhea corresponding to WHO group I (HGT). The ovarian volumes were greater in the PCO and HGT groups than in the OMG group. The serum estradiol and progesterone concentrations correlated more closely with ovarian volumes in the HGT group than in the PCO and OMG groups. The present study failed to demonstrate a lower risk of hyperstimulation in the HGT group in comparison with the PCO and OMG groups. Six patients conceived, and ovarian volumes were greater and serum progesterone concentrations higher during conceptual cycles than during nonconceptual cycles.

The effect of oral contraceptives on hormone profiles of oligomenorrheic adolescent cycles.

Nineteen adolescent girls with oligomenorrhea were studied to evaluate the effect of oral contraceptives (OCs) on hormone profiles, and 19 adolescent girls with regular menstruations served as control subjects. Serum levels of luteinizing hormone and androgens were higher in the oligomenorrheic girls than in the regularly menstruating girls. During the OC treatment the hormone levels of the oligomenorrheic girls decreased, approaching those of the control subjects. During follow-up cycle immediately after stopping the OCs the hormone levels increased rapidly, but in the oligomenorrheic girls the levels of luteinizing hormone, androstenedione, total and free testosterone were still significantly lower at the end of the post-treatment cycle than during the luteal phase of the pre-treatment cycle. The frequency of ovulation decreased to the same magnitude as reported in adults after discontinuation of OCs. No post-pill amenorrhea existed in either group of adolescents.

Endocrine and clinical effects of spironolactone in female hyperandrogenism.

In a double-blind cross-over study, 24 hyperandrogenic women were treated for three months at a time with either spironolactone 100 mg or placebo daily from the 5th to the 21st days of the menstrual cycle. Spironolactone had a slight but statistically insignificant effect on hirsutism when compared with placebo. Slightly more regular menstruation and better follicular growth was noted during spironolactone treatment. Ovulation (defined as a day 21 serum progesterone level of more than 10 nmol/l) occurred in only 12% of spironolactone cycles, as against 28% of placebo cycles. Spotting occurred in one-third of the spironolactone cycles. No significant differences were found between spironolactone and placebo cycles in serum levels of LH, FSH, prolactin, estradiol, progesterone, androstenedione, total testosterone, sex-hormone binding globulin (SHBG), unbound testosterone, dehydroepiandrosterone sulphate (DHEAS), cortisol, potassium and sodium. The average ovarian volume was 13.0 (5.7-21.8) cm3, and no significant differences were found between treatment and placebo cycles. No significant effect of spironolactone could be demonstrated on androgen secretion and the incidence of ovulation.

Serum sex hormone concentrations in adolescent secondary amenorrhoea.

The hormone concentrations of 17 amenorrhoeic adolescent girls, with no apparent environmental factor associated with the secondary amenorrhoea, were evaluated. 28 regularly menstruating adolescent girls served as controls. The clinical characteristics of both groups were similar, except that the amenorrhoeic girls showed clinical signs of androgenicity significantly more often than the regularly menstruating group. The concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, oestradiol, progesterone, testosterone, androstenedione, dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEAS), and sex hormone-binding globulin (SHBG) were determined in weekly blood specimens from the amenorrhoeic girls and during one menstrual cycle from the regularly menstruating girls. The amenorrhoeic girls had significantly higher concentrations of LH, androstenedione and free testosterone than the regularly menstruating girls. The LH/FSH ratio was significantly higher in the amenorrhoeic group than in the control group. The SHBG concentrations were significantly lower in the amenorrhoeic group than in the regularly menstruating group. Evaluation of the clinical signs of androgenicity combined with LH and androgen measurements seems important in the investigation of adolescent menstrual disorders.

Serum sex hormone levels in adolescent girls with polymenorrhoea.

The hormone levels of 13 polymenorrhoeic adolescent girls were evaluated. Twenty-eight adolescent girls with regular menstruation served as controls. Serum concentrations of luteinizing hormone, follicle-stimulating hormone, prolactin, oestradiol, progesterone, testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone-sulphate, and sex hormone binding-globulin were determined in blood samples obtained over one menstrual cycle. In girls with polymenorrhoea the frequency of ovulation was significantly lower than in the control group as estimated on the basis of the progesterone level five days before the onset of menstruation. Low progesterone and oestradiol levels during the late part of the cycle were the main abnormalities of polymenorrhoeic adolescent girls. No differences in the other hormonal parameters were found. The duration of menstrual bleeding was similar in both groups.