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Biomedical subjects

A Tiitinen

Publications and source records attributed to A Tiitinen.

At least 19 recordsLinked to original sources
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

Habitual abortion is accompanied by low serum levels of placental protein 14 in the luteal phase of the fertile cycle.

OBJECTIVE: To study serum levels of placental protein 14 (PP14) in relation to endometrial function in women with a history of habitual abortion. DESIGN: Prospective study. SETTING: Departments I and II of Obstetrics and Gynecology, University Central Hospital of Helsinki, Helsinki, Finland. PATIENTS: Fifty patients (26 primary and 24 secondary habitual aborters) and 38 controls without a history of abortion studied during a regular cycle. RESULTS: Habitual aborters as a whole or when subgrouped into those with normal cycles (n = 40) or with a luteal phase defect (LPD; n = 10) and control women demonstrated a distinct increase in PP14 levels from late follicular to late luteal phases. In the luteal phase, serum PP14 levels were lower in the patients than in the controls (27.2 +/- 3.1 versus 48.5 +/- 10.1 micrograms/L), but the differences in PP14 levels between habitual aborters with or without LPD was not significant (16.3 +/- 4.3 versus 29.9 +/- 3.7 micrograms/L). CONCLUSIONS: Habitual aborters exhibit lower serum PP14 levels in the late luteal phase compared with normal fertile women.

Abortion, Habitual↗
PubMed1995

Endometrial responses to corpus luteum products in cycles with induced ovulation: theoretical and practical considerations.

Products of the corpus luteum have targeted actions on the endometrium. Besides steroid hormones, the corpus luteum produces biologically active substances which may be either unique or shared by the endometrium and other tissues. Here we review selected markers of the corpus luteum and the endometrium as candidates for functional markers of the interplay between the two sites and relative to various treatment modalities. In clinical routine, the assessment of luteal phase is performed by morphological criteria. The timing of endometrial biopsy is important because specimens taken at different stages of the luteal phase give different results. After human menopausal gonadotrophin (HMG) superovulation, there is dyssynchrony in the morphological maturation of endometrial glands and stroma, and a marked difference has been found in endometrial development between progesterone-supplemented and non-supplemented cycles. The expression of steroid hormone receptors in endometrium is affected by ovarian stimulation regimens. After gonadotrophin-releasing hormone analogue/HMG superovulation, the progesterone receptor (PR) has been found less frequently in progesterone-supplemented cycles than in non-supplemented cycles. The relative distributions of oestrogen receptor and PR between epithelium and stroma have been reported to vary according to the number of days of progesterone exposure. Thus, the detection of PR in endometrial glands in the late luteal phase indicates that exposure of the endometrium to the action of progesterone is short. Certain biochemical changes in the uterus are not reflected in endometrial morphology. Under the influence of progesterone, secretory glandular epithelium synthesizes placental protein 14, more recently named glycodelin. Glycodelin inhibits the innate immune system and also has contraceptive actions. Endometrial glands secrete glycodelin into glandular lumen, uterine fluid and blood, where the concentrations rise during the last week of the secretory phase. The effects of various ovarian stimulation protocols on serum glycodelin concentrations are reviewed, along with recent studies on relaxin, prolactin and insulin-like growth factor binding protein 1, all products of the secretory endometrium.

Corpus Luteum↗
PubMed1995

The effect of cryopreservation in prevention of ovarian hyperstimulation syndrome.

OBJECTIVE: To evaluate the effect of elective cryopreservation of all embryos in the prevention of severe ovarian hyperstimulation syndrome in women at increased risk, following superovulation for in vitro fertilisation. DESIGN: Three hundred and ninety women undergoing superovulation for in vitro fertilisation between September 1991 and December 1992. SETTING: University Infertility Clinic, Helsinki, Finland. INTERVENTIONS: Twenty-three women were considered to have an increased risk of developing ovarian hyperstimulation syndrome. They were characterised by more than 20 retrieved oocytes and/or by serum oestradiol levels exceeding 10,000 pmol/l on the day of administration of human chorionic gonadotrophin. Instead of cancelling the cycle the oocytes were harvested and fertilised, and all good quality embryos were cryopreserved. The embryos were thawed and replaced during subsequent natural cycles. MAIN OUTCOME MEASURES: Occurrence of ovarian hyperstimulation syndrome and pregnancy rate. RESULTS: One out of the 23 patients at increased risk developed a moderate degree ovarian hyperstimulation syndrome, while the others had only mild symptoms. Two of the remaining 367 women with no risk developed ovarian hyperstimulation syndrome, both during early pregnancy. Among the 23 patients at increased risk there have been 15 clinical pregnancies after transfer of two to three frozen-thawed embryos in natural cycles, with a 32.6% pregnancy rate. CONCLUSIONS: Withholding embryo replacement and elective cryopreservation of the embryos is effective in preventing severe ovarian hyperstimulation syndrome. After subsequent replacement in natural cycles the implantation rate per embryo is good (22.7%).

Adult↗
PubMed1995

Gonadal function and morphology in non-cirrhotic female alcoholics: a controlled study with hormone measurements and ultrasonography.

OBJECTIVE: To study the occurrence and mechanisms of gonadal dysfunction in women with alcohol abuse. DESIGN: Prospective study. SETTING: Helsinki University Central Hospital. SUBJECTS: Fifteen consecutive chronic female alcoholics without liver cirrhosis admitted for withdrawal treatment, were studied after cessation of alcohol intake. Twelve women had regular menstrual cycles, two appeared to be menopausal and one had hypothalamic amenorrhoea. The women with regular cycles were compared with eleven healthy controls. INTERVENTION: Blood was sampled for hormone measurements three times on cycle days 5 to 7, 11 to 14, and 19 to 22, and ultrasonography was performed on the same days as the first two hormonal studies. MAIN OUTCOME MEASURES: Serum LH, FSH, prolactin, estrone, estradiol, progesterone, testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), the ovarian volume, the follicular diameter, the endometrial thickness. RESULTS: During the luteal phase of the menstrual cycle the serum concentration of testosterone was 65% (p < 0.01) higher and that of progesterone 23% (p > 0.05) lower in patients than in controls. During the follicular phase serum DHEAS level was decreased by 39% (p < 0.05) in patients. Otherwise the serum concentrations of the hormones studied were similar in patients and in controls. As assessed by ultrasonography, patients and controls did not differ with regard to size of the ovaries, follicle development, or the endometrial thickness. CONCLUSIONS: Even heavy alcohol use has only minor permanent effects on ovarian function, at least until development of liver cirrhosis.

Age Factors↗
PubMed1995

Decrease in symptoms, blood loss and uterine size with nafarelin acetate before abdominal hysterectomy: a placebo-controlled, double-blind study.

To evaluate the efficacy and safety of nafarelin before hysterectomy in a prospective placebo-controlled trial, we randomized 188 pre-menopausal women with uterine fibroids (n = 111), menometrorrhagia (n = 58) or pelvic pain (n = 19) to receive either nafarelin (200 micrograms twice daily as a nasal spray) or a placebo for 3 months before abdominal hysterectomy. The data analysis could be performed in 166 women, of whom 107 received nafarelin and 59 a placebo. Nafarelin led to a rise in blood haemoglobin (5.5 g/l) and to a decrease in uterine volume (23.7%). This, however, gave no objective benefit during surgery (similar operative durations and blood losses). The uteri from patients treated with nafarelin (255.5 +/- 12.6 g, mean +/- SD) were significantly lighter (P = 0.029) than those from patients treated with a placebo (346.2 +/- 35.7 g). Histological examination of the fibroids or uteri revealed changes typical for hypo-oestrogenism, but no specific histological pattern could be established. The endometrium was proliferative in 56% and showed mild hyperplastic features in 10% of patients given nafarelin, whereas the respective figures for the placebo group were 41 and 0%. Hot flushes were the most common side-effects, being reported by 61% in the nafarelin group and 35% in the placebo group. Nafarelin can be useful as a pre-surgical adjunct in a patient scheduled for abdominal hysterectomy if there is a need to raise the haemoglobin concentration or to reduce the size of the uterus.

Adult↗
PubMed1994

Serum placental protein 14 concentrations are similar in the first trimester pregnancies of women after pituitary down-regulation with a gonadotrophin-releasing hormone agonist and normal cycles with frozen embryo transfers.

Previous studies suggest that, in pregnancies after in-vitro fertilization (IVF) and embryo transfer following pituitary down-regulation with a gonadotrophin-releasing hormone analogue (buserelin) and ovulation induction with human gonadotrophins, the serum placental protein 14 (PP14) concentration is lower than in normally conceived pregnancies. We studied serum PP14 concentrations in two groups of women: (i) in 17 infertile women whose pregnancy followed IVF and embryo transfer using buserelin (long protocol) and human menopausal gonadotrophin for ovulation induction; (ii) in 15 women whose pregnancy followed transfer of frozen-thawed embryos. Similar PP14 concentrations were found in both groups on days 9-10, 14-15 and 70-77 after human chorionic gonadotrophin administration (buserelin, IVF/embryo transfer) or spontaneous luteinizing hormone surge (frozen-thawed embryo transfer). Our results show that PP14 secretion is not compromised by pituitary down-regulation with buserelin in infertile women with functional ovaries.

Buserelin↗
PubMed1994

Prostaglandin F2 alpha stimulates release of insulin-like growth factor binding protein-3 from cultured human granulosa-luteal cells.

Human ovarian follicular fluid contains a number of insulin-like growth factor binding proteins (IGFBP) of which IGFBP-3 is the most abundant. IGFBP-3 synthesis is growth hormone-regulated. We studied the effect of prostaglandin F2 alpha (PGF2 alpha) on IGFBP-3 secretion by cultured human granulosa-luteal cells from follicular aspirates of women participating in an in-vitro fertilization programme. The IGFBP-3 concentration was measured using a specific monoclonal immunofluorimetric assay. Contrary to a previous report on unstimulated follicles, this study demonstrated a positive correlation between follicular fluid IGFBP-3 concentration and follicular size. PGF2 alpha was found to stimulate in a dose-dependent fashion the secretion of IGFBP-3. Significant (P < 0.05) effects were found at PGF2 alpha concentrations of 10(-8), 10(-7) and 10(-6) M. Because IGFBP-3 inhibits progesterone production stimulated by insulin-like growth factor (IGF)-I, the PGF2 alpha-induced stimulation of IGFBP-3 production may be one of the mechanisms whereby PGF2 alpha exerts its luteolytic effect via the IGF system.

Carrier Proteins↗
PubMed1994

Estrogen replacement does not potentiate gonadotropin-releasing hormone agonist-induced androgen suppression in treatment of hirsutism.

The therapies presently available for treating ovarian hirsutism are not uniformly effective, and therefore, much has been expected from GnRH agonists. These inhibit the secretion of gonadotropins and thereby suppress ovarian function, but at the same time cause hypoestrogenic side-effects. We, therefore, administered goserelin, a long-acting GnRH agonist, for treatment of 20 hirsute women (18 with polycystic ovaries) for 9 months; half of them were randomized to receive cyclic estradiol and medroxyprogesterone replacement from the fourth month onward. Seventeen patients completed the study. Goserelin suppressed ovarian function, as evidenced by a profound reduction in serum estradiol levels. The circulating levels of total testosterone, free testosterone, and androstenedione were lowered at 3 months by 29%, 31%, and 38%, respectively, but there was no effect on the levels of sex hormone-binding globulin (SHBG) or dehydroepiandrosterone sulfate. Ovarian suppression, maintained for the duration of the trial, alleviated hirsutism, as evidenced by a decrease in Ferriman-Gallwey hirsutism scores. Estrogen plus progestin replacement restored estradiol levels and increased SHBG levels, but did not potentiate the therapeutic effect of goserelin or reduce free testosterone levels. Replacement therapy abolished or alleviated hypoestrogenic vasomotor symptoms, but it also caused bleeding and premenstrual symptoms, which necessitated the withdrawal of 3 of 10 women from the treatment. Thus, goserelin is an effective treatment for ovarian hyperandrogenism. Simultaneous estrogen replacement abolishes the hypoestrogenic side-effects, but does not potentiate the effect of goserelin on hirsutism. Interestingly, the estrogen-induced increase in SHBG did not affect free testosterone. Thus, the suppression of gonadotropins, rather than the increase in SHBG, appears to be of primary significance in the alleviation of ovarian hyperandrogenism by estrogens.

Adolescent↗
PubMed1993

Ovarian electrocauterization causes LH-regulated but not insulin-regulated endocrine changes.

OBJECTIVE: We studied the effects of ovarian electrocauterization on the serum levels of luteinizing hormone (LH), testosterone, insulin, sex hormone-binding globulin (SHBG) and insulin-like growth factor binding globulin-1 (IGFBP-1) in women with polycystic ovarian disease (PCOD). DESIGN: Prospective. PATIENTS: Ten women with PCOD admitted to a University Infertility Clinic. MEASUREMENTS: Fasting blood samples for determination of hormone levels were taken during the follicular phase before and one month after laparoscopic ovarian electrocauterization. RESULTS: One month after electrocauterization the serum mean +/- SE LH levels had decreased from 14.4 +/- 1.9 to 10.9 +/- 1.1 U/l (P < 0.05), while the serum insulin levels showed no significant change (10.3 +/- 2.0 and 8.1 +/- 1.3 mU/l). The levels of IGFBP-1 (33.9 +/- 8.2 and 38.4 +/- 13.7 micrograms/l) and SHBG (48 +/- 10.4 and 43 +/- 5.7 nmol/l) showed no significant changes. Testosterone decreased from 3.9 +/- 2.6 to 2.9 +/- 0.3 nmol/l (P < 0.001) and androstenedione from 15.0 +/- 1.2 to 12.0 +/- 1.5 nmol/l (P = 0.05). After electrocautery seven out of ten PCOD patients ovulated either spontaneously (n = 3) or with clomiphene citrate (n = 4), and two of them conceived. CONCLUSIONS: Ovarian electrocautery leads to resumption of ovulatory cycles in some but not all PCOD patients. This effect seems to be mediated by reduction of serum LH and androgen levels, while the insulin-driven pathway via SHBG and IGFBP-1 remains unaffected.

Adult↗
PubMed1993

Recurrent fever associated with progesterone action and persistently elevated serum levels of immunoreactive tumor necrosis factor-alpha and interleukin-6.

We describe two women who suffer from recurrent fever up to 40 C in association with progesterone action and who have continuously elevated serum levels of immunoreactive tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6). In patient 1, recurrent fever began at age 17 yr and has now continued for 11 yr. The patient has had three early pregnancy terminations because of continuous fever and, thereafter, three early pregnancy losses associated with fever. In patient 2, fever first appeared at age 18 yr, and the attacks have now continued for 3 yr. The association between fever and progesterone action is supported by the following facts. 1) The episodes of fever appear in the midluteal phase of the menstrual cycle concomitantly with the highest concentration of serum progesterone. 2) Fever is further exaggerated in early pregnancy. 3) Synthetic progestins induce fever regardless of the day of the menstrual cycle. 4) The progesterone antagonist RU 486 and an agonist of GnRH, nafarelin, are capable of preventing the fever, with no effect on serum cytokine levels. Although the underlying mechanism of elevated TNF alpha and IL-6 levels in our patients remains unknown, the data suggest that these cytokines cooperate with progesterone in exerting a pyrogenic response in the hypothalamic thermoregulatory center.

Acute-Phase Proteins↗