FMR1 repeat analysis in patients with ovarian dysfunction or failure.
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Standard gonadotropin stimulation tests of ovarian function and basal plasma prolactin measurements have been carried out in 151 patients with amenorrhea or severe oligomenorrhea. In 90 of these a standardized multiple pituitary stimulation test, including the prolactin response to thyrotropin releasing hormone, was also performed. There was a tendency for the basal estrogen excretion and the ovarian response to gonadotropin to be lower in patients with hyperprolactinemia. These correlations were weak and did not reach the levels of statistical significance except when compareing the ovariance response in patients with mild hyperprolactinemia to those with moderate or severe hyperprolactinemia. It is concluded that, in women, elevated plasma prolactin levels have little, if any, direct inhibitory influence on the ovariance response to gonadotropins in vivo.
Ovarian hyperstimulation syndrome is a recognized complication of ovulation induction. Abnormalities in liver function have been considered to be a rare manifestation of the severe form of ovarian hyperstimulation syndrome (OHSS). A 28 year old woman with primary infertility underwent ovulation induction and intrauterine insemination. She was diagnosed with moderate OHSS and was followed as an outpatient. Early in her course of treatment she complained of upper right quadrant pain. Her work-up included an upper right quadrant ultrasound which showed only moderate ascites. Liver function tests at that time were elevated in a hepatocellular damage pattern. Liver function test elevations, as well as the ovarian hyperstimulation, resolved spontaneously in 10 days. Transient abnormalities in liver function do not appear to be limited to the most sever forms of OHSS.
For sensitive assessment of thyroid function a TRH stimulation test using 200 micrograms TRH i.v. was routinely performed in 304 women admitted for evaluation and treatment of infertility. In 37 cases (12.2%) the reaction of TSH 30 min after injection of TRH i.v. was enhanced (by definition of a peak TSH level greater than 25 mIU/l), according to mild or subclinical hypothyroidism. Approximately 14 (14/37 = 37.8%) of these patients were found to have slightly elevated serum PRL values (mean PRL greater than 15 ng/ml). Cycle analysis by means of basal body temperature and evaluation of progesterone and oestradiol values, supplied evidence of luteal phase deficiency in 8 and anovulation in 3 cases. Another group of 11 patients with hypothyroidism involved oligo-/amenorrhoea, hirsutism and hyperandrogenaemia. After treatment with 50-150 micrograms l-thyroxine daily for at least 4 to 6 weeks, elevated PRL values significantly decreased (mean level less than 15 ng/ml, p less than 0.01) in 9 out of 12 patients and testosterone levels slightly decreased in 5 out of 8 patients. An improvement of the cyclical ovarian function could be observed by the significant increase of the average progesterone concentration in the luteal phase. During therapy with l-thyroxine, 4 pregnancies occurred. From these results we conclude, that mild hypothyroidism may cause ovarian insufficiency. Assessment of thyroid function should be mandatory in infertile patients with elevated prolactin levels or chronic anovulation.
We studied pubertal status and ovarian function in 21 girls aged 11-21 years who had earlier received 1.2-13 years (median 7 years) high-dose chemotherapy and autologous BMT without TBI for malignant tumors. Ten of them were given busulfan (600 mg/m2) and melphalan (140 mg/m2) with or without cyclophosphamide (3.6 g/m2). Eleven others did not receive busulfan. Twelve girls (57%) had clinical and hormonal evidence of ovarian failure. Among nine others who had completed normal puberty, six had normal gonadotropin levels, one had elevated gonadotropin levels and two had gonadotropin levels at the upper limit of normal. The 10 girls who received busulfan all developed severe and persistent ovarian failure. High-dose busulfan is therefore a major cause of ovarian failure even when given in the prepubertal period. These findings emphasize the need for long-term endocrine follow-up of these patients in order to initiate estrogen replacement therapy.
PROBLEM: Several immunological factors have been associated with diagnostic subpopulations of reproductive failure. It is important to determine a trend of immunological abnormalities among these subpopulations. The purpose of this study is to assist in the selection of treatment for patients suspected of having specific diagnoses of reproductive failure. METHOD OF STUDY: Blood samples from 591 patients were evaluated for the presence of antiphospholipid (APA), antinuclear (ANA), and antithyroid (ATA) antibodies, as well as for lupus anticoagulant (LA), embryotoxic factors (ETF), and elevated levels of natural killer (NK) (CD56+) cells, and all tests were performed as a panel. The patients were grouped into the following diagnostic categories: recurrent pregnancy loss (n = 302), IVF/ET failure (IVFf, n = 122), unexplained infertility (n = 97), ovarian dysfunction (n = 47), and endometriosis (n = 23). The thresholds for positivity and the prevalence of the tested factors among normal healthy populations have been established by testing 100 or more healthy male and female individuals with each one of the tests used (general population control). All tests as panel were performed on 20 normal fertile female individuals as controls (fertile female controls). RESULTS: Of all patients with reproductive failure, 75.6% had at least one abnormal test. The most frequent abnormal result was found to be the elevation of NK (CD56+) cells (37%), followed by ANA (34%), APA (24%), ATA (19%), and ETF (11%). Of the recurrent pregnancy loss patients, 74.2% had at least one positive abnormal result from all of the tests performed: overall, 70% of women with IVF failure had at least one abnormal test; of patients diagnosed with unexplained infertility, approximately 81% had at least one abnormal result; 74.4% of the patients with ovarian dysfunction and 52% of the patients with endometriosis had at least one abnormal result. From normal fertile controls, 10% showed at least one abnormal test result. CONCLUSION: APA, ANA, ATA, ETF, and elevated NK (CD56 ) cells are significantly more prevalent among women experiencing reproductive failure than among the control group and normal healthy individuals.
We compared the residual ovarian function and the fertility of two groups of female patients treated at different times at the authors' institution by neoadjuvant chemotherapy for localized osteosarcoma of the extremities. From 1997 to 2000, one group of 31 females received neoadjuvant treatment according to the IOR 6 protocol, which included high-dose ifosfamide, high-dose methotrexate, adryamycin, and cis-platinum. In this group of patients an oral contraceptive (OC) was given in an attempt to prevent post-chemotherapy ovarian failure. Another group of 90 patients was treated between 1974 to 1995 with the same antiblastic drugs according to similar protocols (IOR 1-IOR 5). These patients did not receive OC or other treatment to protect ovarian function. There were no significant differences between the two groups of patients. Early chemotherapy-induced menopause occurred in 3 out of 19 postpubertal patients who received the OC and in 3 out of 71 postpubertal patients in the control group. In the OC group there were 2 cases of thrombophlebitis. No delay in menarche was seen in prepubertal patients. From statistical evaluation we underline that age and alkylant doses are the most important predictive factors for early menopause and that oral contraceptives during chemotherapy do not protect ovarian function in patients receiving high-dose alkylant based chemotherapy.
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A 30 year old patient with idiopathic thrombocytosis received chemotherapy and developed amenorrhea and secondary ovarian failure. After discontinuation of chemotherapy, she became pregnant and recovered normal ovarian function 6 months after delivery.
The functional status of the hypothalamo-pituitary-gonadal axis was investigated in 127 women with anovulatory disease. Radioimmunoassayable circulating LH, FSH, and prolactin concentrations were measured. An attempt was made to localize the functional lesion by utilizing the following criteria: 1. Hypothalamic function: a) clomiphene test based upon hormonal parameters; b) recording of the pulsatile LH fluctuation (spiking) and of basal FSH. 2. Pituitary function: determination of the gonadotropin reserve by means of a standardized LRH test. 3. Ovarian function: a) measurement of plasma E2 and progesterone levels by RIA; b) gestagen bleeding test. All patients had amenorrhea of up to 14 years duration. A total of 17 hyperprolactinemic patients (13.4%) was found. Eight of these patients never experienced galatorrhea, in 7 only transient galactorrhea was reported, and in 2 cases galactorrhea persisted. All hyperprolactinemic patients were found to be clomiphene non-responders as well as nonspikers. The pituitary LH reserve varied from practically none to normal. Baseline LH was low whereas that of FSH was normal. In accordance with this observation E2 levels, with two exceptions, were found to be in the lower range of normal female concentrations. Thus, all but two patients exhibited gestagen withdrawal bleeding. In conclusion, the hyperprolactinemic anvoluatory syndrome is not necessarily associated with galactorrhea. In all cases of amenorrhea syndromes with or without galactorrhea, hyperprolactinemia should be excluded as it is very often associated with anovulation. The hyperprolactinemic anovulatory syndrome includes the following features: 1. gestagen withdrawal bleeding. 2. subnormal to normal E2 levels. 3. clomiphene nonresponsiveness. 4. LH-hypogonadotropism. 5. lack of LH secretory episodes. 6. FSH-normogonadotropism.
Menopause, conventionally defined as the permanent cessation of menstruation as a result of loss of ovarian follicular activity, is biologically expressed by the collapse of plasma estradiol levels and increased plasma levels of the gonadotrophins FSH (follicle stimulating hormone) and LH (luteinizing hormone). At present, estimation of the ovarian follicle reserve is based on endocrine capacity tests of the ovaries, with increased FSH representing the first sign of exocrine ovarian failure. We report the case of one of our amenorrhoeic patients after chemotherapy, total body radiation and allogenic bone marrow transplantation for acute immunoblastic leukaemia. This patient was included in an in vitro fertilization with oocyte donation (IVF-OD) programme for iatrogenic premature ovarian failure with increased FSH levels. Instead of high levels of gonadotrophins, this young woman recovered spontaneous follicular development, benefited from standard IVF with her own oocytes and brought a twin pregnancy to term. This observation shows that a high FSH level is not a definitive prediction of ovarian exocrine capacity. In young women of child-bearing age such as these wanting a child and showing signs of endogenous estrogen impregnation, evaluation of the existence and quality of follicular development is an important factor.