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Biomedical subjects

A Tiitinen

Publications and source records attributed to A Tiitinen.

At least 73 records · Page 4Linked to original sources

Nationwide data on falling incidence of ovarian granulosa cell tumours concomitant with increasing use of ovulation inducers.

The genesis of ovarian granulosa cell tumours (GCT) has been linked to high gonadotrophin levels, and therefore also to the use of ovulation inducers and combined contraceptive pills (OC). We analysed the occurrence of GCT in the whole of Finland in 1965-1994, the period when ovulation inducers and OC became available. All women with GCT were traced from the Finnish Cancer Registry. The numbers of courses of clomiphene citrate and gonadotrophin (human menopausal gonadotrophin: HMG) and number of courses of OC used in Finland during the same period were calculated from sales statistics on these agents. In 1965-1994, 590 patients contracted GCT. The incidence of GCT declined by nearly 40% from 0.74/100000 in 1965-1969 to 0.47/100000 in 1985-1994, a fall occurring at the same time that the use of clomiphene citrate increased 13-fold, that of HMG 200-fold and that of OC 5-fold. Our nationwide data on the incidence of GCT falling concomitantly with increasing use of ovulation inducers can be seen as one piece of evidence that ovulation inducers are unlikely to cause GCT.

Adolescent↗

Obstetric and perinatal outcome after oocyte donation: comparison with in-vitro fertilization pregnancies.

The obstetric and perinatal outcome in 51 oocyte donation pregnancies (61 infants) was compared with that of a control group of standard in-vitro fertilization (IVF) patients (97 pregnancies, 126 infants). The oocyte recipients (mean +/- SD age 33.5+/-4.7 years) included 39 women with ovarian failure and 12 women with functioning ovaries. In oocyte recipients, first trimester bleeding (53%) occurred significantly more often than in IVF mothers (31%, P < 0.01). Pregnancy-induced hypertension was observed in 31% of oocyte recipients compared with 14% in IVF mothers (P < 0.05). There was no difference in the duration of pregnancies or in the preterm delivery rate between the two groups. When restricting analysis to singleton pregnancies, 63% of oocyte recipients were hospitalized in the antenatal period compared with 29% in the IVF group (P < 0.001). The Caesarean section rate was 57% in the oocyte donation group and 37% in the IVF group (P < 0.05). Birthweight in singleton pregnancies was similar in both groups. The perinatal mortality rate was 3.3% in the oocyte donation group and 0% in the IVF group. In conclusion, oocyte donation pregnancies are associated with an increased risk compared with IVF pregnancies, but the complications are usually manageable and most oocyte recipients experience a good pregnancy outcome.

Adult↗

Health and development of children born after oocyte donation compared with that of those born after in-vitro fertilization, and parents' attitudes regarding secrecy.

The health, growth and development of a cohort of children (n = 59) aged 6 months to 4 years and born after oocyte donation (OD) was compared with that from a group of children born after in-vitro fertilization (IVF) (n = 126). The study was performed by questionnaire, and the response rate was 100% in the OD group and 95% in the IVF group. All OD children were healthy. Three IVF children had a neurological disorder. Surgical intervention had been carried out in 8% of the OD and 13% of the IVF children. Height and weight development were normal, and eating and sleeping disorders were uncommon in both groups of children. The IVF mothers more often expressed concern about the child's behaviour than did the OD mothers. Thirty-eight percent of the OD parents and 60% of the IVF parents intended to tell the child about the nature of its conception (P < 0.01). Although oocyte recipients appear to have more complications during their pregnancies than conventional IVF patients, the general health status of OD children aged <5 years is at least as good as that of IVF children. Growth and development in both groups of children is similar to that of the general population.

Body Height↗

Comparison of effects of tamoxifen and toremifene on bone biochemistry and bone mineral density in postmenopausal breast cancer patients.

Antiestrogens are used in the treatment, and sometimes even in the prophylaxis, of breast cancer. Tamoxifen is the most commonly used antiestrogen, but toremifene is gaining in popularity. We compared here the effects of tamoxifen and toremifene on bone metabolism and density in 30 postmenopausal patients with breast cancer, who were randomized to receive tamoxifen (20 mg/day, n = 16) or toremifene (40 mg/day, n = 14) for 1 yr. Biochemical markers of bone resorption [urinary hydroxyproline, serum cross-linked carboxyterminal telopeptide of type I collagen, urinary cross-linked aminoterminal telopeptide of type I collagen (NTx)] and bone formation [serum bone-specific alkaline phosphatase, osteocalcin, and aminoterminal and carboxyterminal propeptide of type I procollagen] were assessed before treatment and at 6 and 12 months of the antiestrogen regimen. Bone mineral density (BMD) in the lumbar spine and proximal femur (neck, trochanter, and Ward's triangle) was measured using dual-energy x-ray absorptiometry before treatment and at 12 months of treatment. Urinary NTx decreased after 6 months' use of tamoxifen (mean fall: 33%) and of toremifene (mean fall: 16%). Use of tamoxifen was associated with a significant decrease in osteocalcin (mean fall: 25%) and aminoterminal propeptide of type I procollagen (mean fall: 22%), whereas toremifene failed to influence these markers. Tamoxifen increased BMD, on average, by 2% in the lumbar spine, 1% in the femoral neck, and 5% in Ward's triangle. Toremifene failed to increase BMD at any site measured, and in contrast, a slight trend toward a fall (-0.3 to -0.9%) in BMD was seen in patients treated with toremifene. Falls in urinary NTx, from baseline to 6 months, correlated significantly with changes in the lumbar spine BMD (r = -0.57, P = 0.0002) in the whole patient series. We conclude that tamoxifen (20 mg/day) increases BMD in postmenopausal breast cancer patients, whereas toremifene (40 mg/day) merely prevents the increasing age-associated fall in BMD. More prolonged studies on bone metabolism, comparing these two antiestrogens, are needed; but even now, clinicians should be aware of these differences between tamoxifen and toremifene.

Aged↗

Detection of Chlamydia trachomatis antibodies by 2 novel tests: rELISA and peptide EIA.

The performance of 2 newly developed enzyme immunoassays (EIAs) intended for the routine serological diagnosis of chlamydial infections was evaluated. rELISA is based on a recombinant lipopolysaccharide antigen which detects chlamydia genus-specific antibodies, and Chlamydia trachomatis EIA is based on a peptide derived from major outer membrane protein and is therefore species-specific. Both tests distinguished patients with tubal factor infertility (TFI) or pelvic inflammatory disease (PID) from the controls. The prevalence of IgA antibodies was higher for the PID patients than for the TFI patients; the finding indicates a more active state of infections for the PID patients. Furthermore, C. trachomatis EIA detected more IgG antibodies in the TFI patients than in patients with non-tubal factor infertility. In conclusion, rELISA detected chlamydial antibodies in general, and C. trachomatis EIA detected species-specific antibodies. These EIA tests may be useful in the serodiagnosis of chlamydial infection.

Adult↗

Obstetric outcome in patients with unexplained infertility: comparison of treatment-related and spontaneous pregnancies.

BACKGROUND: The aim of this study was to determine the long-term prognosis of fecundity among couples with unexplained infertility and to compare pregnancy course and outcome in spontaneous versus treatment-related pregnancies. METHODS: A prospective follow-up study of 70 couples with a diagnosis of unexplained infertility. All couples had participated in a study at the Helsinki University Central Hospital where the effectiveness was compared with intrauterine insemination, direct intraperitoneal insemination or timed intercourse, each combined with superovulation. The follow-up was carried out by collecting all available information on treatment-related and spontaneous pregnancies from hospital records and questionnaires mailed to these same women 6 years later. RESULTS: Of 70 couples, 45 (64.3%), conceived during the follow-up period. Of all 83 pregnancies, 50 (60.2%) began spontaneously and 33 (39.8%) with infertility treatment. Rate of multiple deliveries was 25% in treatment-related pregnancies, but only 2.8% in spontaneous pregnancies (p<0.05). Mean birthweight among singleton pregnancies was 3 120 grams in treatment-related, and 3387 grams in spontaneous pregnancies (p<0.05). The rate of small-for-gestational-age (<-2 s.d.) and preterm births (before 37 completed weeks) in both groups was equal. CONCLUSIONS: The long-term prognosis of couples with unexplained infertility was good, and many of the pregnancies began spontaneously. The birthweight of singleton neonates in treatment-related pregnancies was lower than in spontaneously conceived pregnancies, but otherwise perinatal outcome was similar.

Female↗

Comparison of buserelin and nafarelin in IVF cycles and in subsequent frozen-thawed embryo transfer cycles.

OBJECTIVE: To compare two gonadotropin-releasing hormone agonists for down-regulation prior to superovulation in in vitro fertilization/embryo transfer treatment. METHODS: Infertility patients (n=181) were randomized to receive buserelin (1200 microg/day, n=90) or nafarelin (800 microg/day, n=91) intranasally starting in the luteal phase. Serum levels of LH, estradiol and progesterone were measured during the treatment. The cycles were compared with regard to number of oocytes, fertilization and implantation rates and achieved pregnancies. RESULTS: Serum LH was lower after two weeks on buserelin: 1.8 (1.3-2.4) IU/L (median, with lower and upper quartile in parenthesis), than after nafarelin: 2.6 (1.8-4.0) IU/L, (p=0.0001). No other differences in serum hormone levels could be detected. More oocytes were recovered in the buserelin group: 13.0 (8.0-19.0) vs 11.0 (6.8-15.0), (p=0.046), but the fertilization rate was higher in the nafarelin group (49.9%, vs 45.1%, p=0.023). Implantation rate was higher in the nafarelin group (26.28% vs 15.5%, p=0.030), but there were an equal number of deliveries in both groups (20.9% vs 15.6% per started stimulation, p=0.420). In the subsequent frozen-thawed embryo transfer cycles the implantation rate was 21.1% (nafarelin group) and 10.6% (buserelin group, p=0.067), the pregnancy rate/ET was 31.7% and 17.0% (p=0.107) and the delivery rate was 22.0% and 10.6% (p=0.148), respectively. CONCLUSIONS: Differences exist in IVF-cycles down-regulated with buserelin or nafarelin which might affect embryo quality and treatment outcome.

Adult↗

Evidence of interplay between plasma endothelin-1 and 17 beta-estradiol in regulation of uterine blood flow and endometrial growth in infertile women.

OBJECTIVE: To determine the effects of gonadotropin-induced ovarian stimulation on the plasma levels of endothelin-1 as well as on uterine blood flow and endometrial thickness. DESIGN: Controlled cross-over clinical study. SETTING: Academic research environment. PATIENT(S): Eighteen volunteer infertile women (31.4 +/- 2.5 years, mean +/- SE) participating in an IVF-ET program. INTERVENTION(S): Transvaginal Doppler ultrasound was performed and blood samples were collected 4 days after the LH surge in a spontaneous cycle and 4 days after hCG administration in a subsequent gonadotropin-stimulated cycle. MAIN OUTCOME MEASURE(S): Plasma levels of E2, P, and endothelin-1; uterine artery pulsatility index; and endometrial thickness. RESULT(S): Stimulated cycles were associated with significantly higher E2 levels (101.0 +/- 10.2 versus 723.5 +/- 57.3 pg/mL [conversion Factor to SI unit, 3.671]; spontaneous versus stimulated), thicker endometrium (9.2 +/- 2.5 versus 11.4 +/- 2.9 mm), and lower endothelin-1 levels (2.5 +/- 0.1 versus 2.1 +/- 0.1 pg/mL [conversion factor to SI unit, 0.4]) and pulsatility index (3.22 +/- 0.12 versus 2.63 +/- 0.08) than spontaneous cycles. Endothelin-1 correlated negatively with E2 (r = -0.38), but not with P or pulsatility index. Differences in endothelin-1 and endometrial thickness between spontaneous and stimulated cycles correlated negatively (r = -0.56) with each other. CONCLUSION: Our results suggest an inhibitory role for E2 in the release of endothelin-1, which could be a factor in the regulation of uterine and endometrial blood flow.

Adult↗

Levonorgestrel-releasing intrauterine device can be used in oocyte donors during ovarian stimulation.

Seven oocyte donors with a levonorgestrel-releasing intrauterine device (LNG-IUD) in situ (group A) underwent ovarian stimulation with human menopausal gonadotrophin (HMG) after goserelin down-regulation, in eight treatment cycles. The donors in a control group (group B, n = 16) were comparable in age, body mass index and parity characteristics. There were no statistically significant differences in response to ovarian hyperstimulation between the two groups. The number of oocytes recovered was 12.4 +/- 5.1 (SD) following stimulation with 27.9 +/- 9.3 ampoules of HMG over 11.2 +/- 1.3 days in group A. Following stimulation with 26.2 +/- 6.3 ampoules of HMG over 11.0 +/- 1.0 days, the number of oocytes collected was 13.9 +/- 10.4 in group B. The fertilization rate (2PN/cell) of cells in group A was 63% (62/99) and in group B, 53% (117/220, not significant). The cleavage rate of cells in group A (60%, 59/99) was significantly higher than in group B (47%, 104/220) (P <0.05). On average, two embryos were transferred per cycle. In group A, the pregnancy rate per transfer was 40% (4/10) and in group B, 29% (6/21; not significant). In conclusion, LNG-IUD can be used as a contraceptive method during ovarian stimulation of volunteer oocyte donors.

Adult↗

Superovulation combined with insemination or timed intercourse in the treatment of couples with unexplained infertility and minimal endometriosis.

BACKGROUND: To compare intrauterine insemination (IUI), direct intraperitoneal insemination (DIPI), and timed-intercourse (TI), each combined with superovulation, in the treatment of couples with unexplained infertility, including couples with minimal endometriosis. METHODS: A retrospective analysis of 233 superovulation cycles in 70 couples with unexplained infertility or minimal endometriosis. Stimulation protocol, pregnancy rate, pregnancy outcome, and complications of treatment were analyzed. RESULTS: The pregnancy rare was 8.6% per cycle and 28.5% per couple. A majority of all treatment pregnancies (85%) occurred during the first four cycles of treatment. The duration of infertility did not influence the pregnancy rate. The pregnancy rate in patients with unexplained infertility was higher, but not significantly, than in patients with minimal endometriosis (27.7% versus 18.4%). No predictive marker for successful stimulation was found, except for the higher luteal progesterone level in cycles resulting in pregnancy. The multiple pregnancy rate was high: 30% of all pregnancies and 40% of all deliveries were multiple. CONCLUSIONS: Superovulation in combination with insemination or intercourse is effective and is still recommended in the treatment of couples with unexplained infertility.

Adult↗

Does ovarian stimulation affect uterine artery impedance?

PURPOSE: We evaluated the effect of induction of ovulation on uterine perfusion. METHODS: In 42 infertile women transvaginal color Doppler was performed at days 16-21 of a spontaneous ovulatory cycle and prior to embryo transfer in an in vitro fertilization (IVF) cycle. Indication for treatment was mainly tubal or unexplained infertility. RESULTS: Uterine artery pulsatility index was significantly (P < 0.001) lower in IVF than in natural cycles, 3.24 +/- 0.72 2.64 +/- 0.53 (mean +/- SD), with a mean reduction of 18%. The reduction was higher, although not significantly, in the women who conceived (20%) than in those who did not (15%), and in those with a basal PI > 3.0 (20%) as opposed to those with normal values (16%). The percentage reduction correlated with patient age and with estradiol concentration, number of follicles, and oocytes recruited. CONCLUSIONS: Induction of superovulation reduces impedance to flow in the uterine circulation. The amplitude of this effect appears to be regulated partially by patient age and by effectiveness of ovarian stimulation.

Adult↗

Transvaginal Doppler study of uterine artery blood flow in in vitro fertilization-embryo transfer cycles.

OBJECTIVE: To verify whether uterine artery impedance, measured as pulsatility index and resistance index is related to the outcome of in IVF-ET cycles. DESIGN: Prospective study of infertile women participating in an IVF-ET program. SETTING: University Hospital. PATIENTS: Two hundred women (24 to 40 years of age), who had one to three good quality embryos transferred to the uterus after a standardized IVF cycle. INTERVENTION: Transvaginal color Doppler and a blood sample on the day of ET. MAIN OUTCOME MEASURES: Uterine artery pulsatility index and resistance index, endometrial thickness, serum E2 and P concentrations, clinical pregnancy rate (PR). RESULTS: Pulsatility indices and resistance indices were lower in conception (2.45 +/- 0.54 and 0.85 +/- 0.04, respectively) than in nonconception cycles (2.66 +/- 0.39 and 0.87 +/- 0.04, respectively), although the overlap of the values is considerable. Overall PR was 35% per ET, and it decreased significantly when pulsatility index was > 3.0 (15%) and resistance index > 0.92 (13%), being lowest when pulsatility index was > 3.3 and resistance index > 0.95 (10%). Such a high impedance was detected in 9% of nonconception cycles. CONCLUSION: In IVF-ET cycles the uterus is likely to be unreceptive when uterine artery pulsatility index is > 3.3 and resistance index > 0.95 before ET, but this occurs only in 9% of the cycles.

Adult↗

Ectopic pregnancy after in-vitro fertilization is characterized by delayed implantation but a normal increase of serum human chorionic gonadotrophin and its subunits.

We studied the dynamics of serum human chorionic gonadotrophin (HCG) and its free alpha (HCG alpha) and beta (HCG beta) subunits in 49 early pregnancies achieved by in-vitro fertilization (IVF) and embryo transfer. Of the 49 early pregnancies, nine were normal singleton pregnancies, 11 were twin pregnancies, 11 were ectopic, eight ended in a clinical (spontaneous) abortion and 10 ended in a preclinical abortion. The HCG, HCG alpha and HCG beta concentrations in serum were measured on days 12, 19 and 26 after embryo transfer. Most ectopic pregnancies could be distinguished from singleton (and twin) pregnancies on the basis of low HCG concentrations by 12 days after embryo transfer, but clinical abortions could not be distinguished from singleton pregnancies. In general, the measurement of HCG alpha and HCG beta and the molar ratios of the various forms provided only marginal additional value to that obtained from HCG, but on days 19 and 26 after embryo transfer HCG alpha was the most sensitive indicator of a normal pregnancy after IVF and embryo transfer. We conclude that in ectopic pregnancies the concentrations of HCG, HCG alpha and HCG beta increase as expected but 1.5 days later than in normal pregnancies. This appears to be the result of a delay in implantation.

Abortion, Spontaneous↗

High bone density in hyperandrogenic women: effect of gonadotropin-releasing hormone agonist alone or in conjunction with estrogen-progestin replacement.

We studied 20 hirsute patients with high levels of serum testosterone (T), calculated free T, androstenedione, and dehydroepiandrosterone sulfate and 19 age-matched nonhirsute normoandrogenic control women. The bone mineral density (BMD) in the lumbar spine, femoral neck, and trochanter major region in hirsute patients was higher than that in the controls. BMD in the lumbar spine and proximal femur correlated positively with the body mass index and with serum T and free T in hyperandrogenic women and the whole study group, but not with serum androstenedione or dehydroepiandrosterone sulfate levels. The hirsute women were treated with a GnRH agonist (goserelin, 3.6-mg implant) for 9 months. After the first 3 months of treatment, half of the patients were randomized to receive estrogen-progestin replacement therapy (HRT), and the other half served as controls. After the first 3 months of trial, BMD was unaffected, and the urinary output of collagen pyridinoline, deoxypyridinoline cross-links, and hydroxyproline (all markers of bone resorption) were increased, but serum markers, the carboxy-terminal telopeptide of type I collagen (marker of bone resorption) and that of bone-specific alkaline phosphatase (marker of bone formation) did not change. After 9 months of goserelin treatment, the lumbar spine had lost 5.4% of its BMD (P < 0.01), but regained bone density 6 months after cessation of treatment. Addition of HRT protected the spine and trochanter major against bone loss. The changes in serum telopeptide and urinary output of pyridinoline and deoxypyridinoline after 3 months of treatment (from prestudy levels) correlated with the decrease in BMD in the femoral neck at 9 months. In conclusion, our data show that patients with ovarian androgen excess 1) have high BMD, 2) lose bone during 9 months of treatment with GnRH agonist, 3) show a decrease in bone density preceded by biochemical alterations in bone metabolism at least 6 months earlier, and 4) can have their bone loss prevented by add-back HRT.

Adult↗