Hysteroscopy--the womb revisited.
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Dilatation and Curettage↗
Biomedical subjects
C M March
Publications and source records attributed to C M March.
Hysteroscopy as an aid to diagnosis in female infertility.
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Endoscopy↗
A decade's experience with an individualized clomiphene treatment regimen including its effect on the postcoital test.
During a 10-year period, 428 women received clomiphene citrate according to a graduated therapeutic regimen in which the dose of clomiphene and the laboratory studies were individualized according to each patient's history, examination and response. Of the 428 patients, 85.3% ovulated and 42.8% conceived. The great majority of those who conceived did so during the first three ovulatory cycles. There was no evidence that clomiphene therapy was associated with the induction of another cause of infertility. Overall, 88.2% of those with no other causes for infertility who ovulated also conceived. However, only 7.8% of those who had one or more factors in addition to anovulation became pregnant. There was no evidence that clomiphene adversely affected the postcoital test, as only 15% of the patients had poor cervical mucus. The low rate of complications of this treatment, 5.1% cyst formation as well as the 14% abortion rate and the 2.6% congenital anomaly rate and the excellent gestational outcome in those who conceived support the use of this treatment regimen.
17-Ketosteroids↗
The modulating role of obesity and 17 beta-estradiol (E2) on bound and unbound E2 and adrenal androgens in oophorectomized women.
17 beta-Estradiol (E2) pellet replacement therapy for oophorectomized women has been shown to be safe and effective. Some investigators have advocated the addition of testosterone (T) pellets for oophorectomized women. This study was carried out to measure the level of androgens in oophorectomized women with and without E2 pellets. The possible modulating role of E2 upon adrenal androgens was investigated as well as the effects of obesity on bound and unbound serum levels of E2 and T. Seven obese patients and eight nonobese normal patients with E2 pellets were compared to nine oophorectomized age- and weight-matched control women not receiving estrogen. Obese patients had higher levels of androstenediol (Adiol) and androstenedione (A) than nonobese patients, yet compared to oophorectomized controls, nonobese patients had higher levels of dehydroepiandrosterone sulfate (DHEA-S) and Adiol. As a group, patients with E2 pellets had higher levels of DHEA-S, Adiol A, and unbound T compared to oophorectomized controls, and their Adiol and total and unbound T levels were similar to those of premenopausal females. Obese patients had lower levels of total E2, yet a higher percentage of unbound E2, resulting in unbound E2 levels which were similar to those of the nonobese women. Unbound T was higher in obese patients compared to the nonobese women and oophorectomized controls. In conclusion, these data suggest that 1) there may be a modulating role of E2 on adrenal androgens exemplified by an increased serum level of delta 5-3 beta-ol androgens in women with E2 pellets, 2) supplemental T implants for oophorectomized women may not be necessary, and 3) obese women with pellets have higher levels of Adiol, A, and unbound T then nonobese women and therefore have a higher ratio of androgen to estrogen.
Adult↗
Clomiphene and dexamethasone in women unresponsive to clomiphene alone.
Twelve oligomenorrhic women with polycystic ovary syndrome (PCO) in whom clomiphene (250 mg daily for 5 days) and 10,000 IU human chorionic gonadotropin had failed to induce ovulation were treated with clomiphene and dexamethasone. Eight of the 12 women underwent complete hormonal assessment during treatment. Six of the 12 ovulated and 1 conceived. Serum total and unbound estradiol and testosterone (T), serum dehydroepiandrosterone sulfate (DHEA-S), sex hormone binding-globulin binding capacity (SHBG-BC), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL) were measured during clomiphene and dexamethasone therapy. SHBG-BC increased in response to clomiphene whether or not ovulation occurred. After treatment with clomiphene and dexamethasone there was a significant decrease in serum T, unbound T, and DHEA-S 2 weeks after dexamethasone administration, but there were no change in LH, FSH, or PRL. In patients who ovulated after clomiphene and dexamethasone, T and unbound T increased again after clomiphene was begun despite the continuation of dexamethasone. The women who ovulated after clomiphene and dexamethasone treatment had significantly higher pretreatment levels of DHEA-S than those who did not ovulate. Clomiphene and dexamethasone treatment may be beneficial to women who have elevated levels of DHEAS and who fail to ovulate with maximum doses of clomiphene.
Anovulation↗
Clinical and laboratory predictors of clomiphene response.
A prospective study was carried out on 158 anovulatory women for the purpose of finding parameters that might predict the clomiphene dose at which ovulation would occur. Both body weight and obesity were positively correlated with the dose required to achieve ovulation (P less than 0.05). Once ovulation occurred, obesity did not affect the ability to conceive. Fifty-eight women who ovulated with various doses of clomiphene, including six women who failed to ovulate, had hormonal measurements performed prior to treatment. Compared with normally ovulating controls, serum luteinizing hormone (LH), the ratio of LH to follicle-stimulating hormone (FSH), serum androgens, unbound testosterone, and unbound estradiol were elevated and sex hormone binding globulin-binding capacity (SHBG-BC) significantly lower in women receiving clomiphene. Although the ovulatory dose of clomiphene was positively correlated with both weight and obesity, neither weight nor any laboratory parameter could accurately predict the clomiphene response.
Androgens↗
Longitudinal evaluation of patients with untreated prolactin-secreting pituitary adenomas.
A group of 43 patients with galactorrhea, hyperprolactinemia, and radiographic evidence of pituitary adenomas were followed from 3 to 20 years. Initial polytomography and computerized tomographic (CT) scans revealed no evidence of extrasellar extension. Serum levels of prolactin (PRL) were measured at 6 month intervals, and visual fields were assessed annually. Polytomograms and CT scans were repeated every 9 to 36 months. During the period of follow-up, CT scans (but not polytomograms) indicated tumor enlargement in two patients, both of whom underwent selective transsphenoidal removal of the tumor. Polytomograms and CT scans did not show any change in the other 41 patients, and three of them have resumed normal menses, are no longer lactating, and have normal PRL levels. The initial results of this ongoing study indicate that most patients with small pituitary adenomas can be followed with annual CT scans with or without medical therapy, and that surgical treatment should be reserved for those patients with large tumors, those with visual-field loss, and those who show signs of enlargement of the tumor.
Adenoma↗
Gestational outcome following hysteroscopic lysis of adhesions.
Thirty-eight infertile women conceived 43 times following treatment for intrauterine adhesions (IUA). Adhesions were classified as being minimal in 7 women, moderate in 20 others, and extensive in 11. All women underwent hysteroscopy with division of all adhesions utilizing miniature scissors and high-dose estrogen treatment for 2 months. In addition 35 of the 38 women had either an intrauterine contraceptive device or a Foley catheter placed to prevent readherence of the walls, and 31 women had the uterine cavity investigated again prior to attempting a pregnancy. Prior to treatment for IUA only 16.7% of all pregnancies in those women with no other cause for pregnancy loss resulted in the delivery of a living infant. However, following treatment 87.2% of these pregnancies resulted in the delivery of a viable infant (P less than 0.001). No instances of placenta accreta occurred, and manual removal of the placenta was not required. Division of adhesions under hysteroscopic control together with the adjunctive measures utilized is superior to all other methods of therapy for IUA and should replace them.
Abortion, Spontaneous↗
Feedback effects of estradiol and progesterone upon gonadotropin and prolactin release.
The relationship between estradiol- and progesterone-mediated gonadotropin release and steroid-induced changes in prolactin levels was investigated in an improved human experimental model. Three women who had undergone bilateral ovariectomy were studied after they had received a subcutaneous implant of one 25-mg estradiol (E2) pellet. Serum E2 levels remained between 60 and 125 pg/ml, and serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations were within the normal or slightly elevated range. Serum prolactin (PRL) levels were normal. Each woman received intramuscular injections of gradually increasing doses of estradiol benzoate (E2B) alone and in combination with progesterone (P) in 7 different experiments. An E2B-induced rise in E2 levels comparable to that observed at midcycle elicited a clearly defined LH surge but no change in FSH and PRL. Rising E2 concentrations followed by increasing P levels caused LH and FSH release but no change in PRL. When only P was administered or when serum P levels rose concomitantly with E2 levels, PRL and gonadotropin levels remained unchanged. These data indicate that a surge of E2 similar to that observed at midcycle triggers an acute release of LH only. Moreover, P levels commensurate with those found at mid-cycle facilitate an E2-mediated LH release and induce a concomitant peak in FSH. The lack of a significant increase in PRL levels suggests that different mechanisms are responsible for the pituitary release of PRL and gonadotropins.
Adult↗
Urinary estradiol-17-beta-glucuronide assay for gonadotropin therapy.
To investigate the possibility of using urinary estradiol-17 beta-glucuronide (E2-17G) measured by direct radioimmunoassay to monitor ovulation induction with human menopausal gonadotropin (hMG), serum estrogen and urinary E2-17G levels were determined daily by 21 women treated with hMG for a total of 32 treatment cycles. Urinary E2-17G was measured in 24-hour and overnight specimens. A significant correlation was found between serum estrogens (primarily estradiol) measured by radioimmunoassay without preceding chromatography and urinary E2-17G excretion measured at 24 hours and overnight. The correlation was not significantly improved by correcting the 24-hour and overnight urinary E2-17G excretion levels with creatinine measurements. Although there was significant correlation between serum estrogens and urinary E2-17G measured by direct radioimmunoassay, the urinary E2-17G concentrations observed when serum estrogens levels indicated preovulatory follicle maturation (ie, at serum estrogens levels between 500 and 1000 pg/ml) varied so much that a clinical decision to trigger or not to trigger ovulation with human chorionic gonadotropin could not be reached in each case. These data indicate that significant correlation is not the only prerequisite for a new method to replace a proved procedure. Further studies are required to determine the reliability of monitoring hMG therapy with direct E2-17G radioimmunoassays in overnight urine collections.
Adult↗
Subdermal estradiol pellets following hysterectomy and oophorectomy. Effect upon serum estrone, estradiol, luteinizing hormone, follicle-stimulating hormone, corticosteroid binding globulin-binding capacity, testosterone-estradiol binding globulin-binding capacity, lipids, and hot flushes.
Subderman estradiol (E2) pellets (25 mg) were inserted immediately after hysterectomy and oophorectomy in 22 menstruating women, ages 29 to 50 years. Serum samples were obtained daily for 7 days, weekly for 4 weeks, and at monthly intervals for 6 months. Although there was significant variation between patients, E2 levels remained within the follicular phase range, averaging 50 to 70 pg/ml for 3 months, and then slowly declining to a mean of 37 pg/ml at 6 months, when new pellets were inserted. Over the entire study period, the E2:estrone (E1) ratio was greater than unity. Subdermal E2 pellets limited the rise in luteinzing hormone (LH) and follicle-stimulating hormone (FSH) after gonadectomy and the levels of LH and FSH 6 months after the insertion of E2 pellets were significantly lower (p < 0.01) than in 20 postmenopausal women who had undergone oophorectomy and whose serum E2 levels were less than 20 pg/ml. Serum corticosteroid binding globulin-binding capacity (CBG-BC) and serum testosterone-estradiol binding globulin-binding capacity (TeBG-BC) remained unchanged with E2 pellets. Although high-density lipoprotein-cholesterol increased significantly (p < 0.05), low-density lipoprotein-cholesterol, total cholesterol, and triglycerides were unaffected, except for a rise in triglycerides in three older women with diabetes mellitus and hypertension. There were no complaints of severe hot flushes. Women who had vasomotor symptaoms had mild or moderate flushes that occurred at 5 or 6 months after replacements of the pellets. Thus, E2 pellets are an effective form of parenteral estrogen replacement therapy and offer both practical and theorteical advantages over other forms of estrogen.
Adult↗
Febrile morbidity following hysterosalpingography: identification of risk factors and recommendations for prophylaxis.
Although previous large series have reported that from 0.3% to 1.3% of patients undergoing hysterosalpingography (HSG) develop infectious morbidity, our impression was that the incidence was higher among our patients. Therefore the records of 448 consecutive healthy women who underwent HSG were examined. Within 24 hours after the HSG, 14 of these 448 patients (3.1%) developed fever and pelvic peritonitis requiring hospitalization and treatment with parenteral antibiotics, a significantly greater frequency than reported elsewhere (P less than 0.01). Traditional laboratory tests failed to predict patients at risk, and prophylactic antibiotics effective against aerobic organisms could not protect against this complication. However, it was possible to design a scoring system based on specific findings in the history and previous physical examinations that was capable of identifying patients who would subsequently become infected. The clinical sensitivity of this scoring technique is 57%, clinical specificity 99%, and test efficiency 97%. It is suggested that in view of the major risk of post-HSG infection in certain identifiable women and because of the impact of this complication on their future fertility, hysterosalpingography should not be performed in those patients determined to be at high risk. In women at lowest risk, the procedure is safe. Finally, in patients assigned an intermediate risk-score, the risk-benefit ratio must be carefully weighed and discussed with the patient, and prophylactic antibiotics with anaerobic coverage should be considered.
Adolescent↗
A comparison of clinical and laboratory methods in monitoring human menopausal gonadotropin therapy.
Twenty infertile, anovulatory women were treated with human menopausal gonadotropin (hMG) for a total of 61 treatment cycles. Cervical scores (all cycles) and vaginal maturation indices (23 cycles) were compared with serum concentrations of total immunoreactive estrogens to determine their clinical efficacy in monitoring hMG treatment. All courses of therapy were judged to have induced ovulation. Singleton pregnancies occurred in nine patients, and one patient conceived twice. All pregnancies were uncomplicated. There was good clinical correlation between cervical score and increasing estrogen levels in approximately one-third of the cycles. Most of these good correlations occurred in patients with low estrogen status. Very poor correlation was found with vaginal cytologic changes. Therefore, in conjunction with serum estrogen determinations, the cervical score is a safe and less expensive means of monitoring hMG therapy in selected patients.
Adult↗
Galactorrhea and pituitary tumors in postpill and non-postpill secondary amenorrhea.
One hundred sixty-seven women with secondary amenorrhea were observed from six months to four years. In 66 patients, the amenorrhea followed the discontinuation of oral contraceptives (postpill) while in the remaining 101 the amenorrhea was not temporally pill related (non-postpill). Galactorrhea was present in 43 (65%) of those with postpill amenorrhea and in 32 (32%) of those with non-postpill amenorrhea (p less than 0.001). Tomography of the sella turcica was performed in the 75 women with galactorrhea and in the 35 without galactorrhea who did not have withdrawal uterine bleeding following progesterone administration and who had low or normal serum follicle-stimulating hormone levels (hypothalamic-pituitary failure). Forty of the 75 patients with amenorrhea and galactorrhea had radiographic evidence of a pituitary tumor whereas only eight of 35 patients with hypothalamic-pituitary failure without galactorrhea had an abnormal sella turcica (p less than 0.01). The incidence of radiographic abnormalities in those with galactorrhea was similar in both the postpill and non-postpill groups.
Adolescent↗
Gonadotropin insufficiency in patients with thalassemia major.
To elucidate whether the cause of sexual maturational arrest in thalassemia major is of hypothalamic or pituitary etiology, three female and two male patients were extensively studied. After the iv administration of 150 micrograms gonadotropin-releasing hormone (GnRH) and 500 micrograms of TRH, all patients demonstrated a minimal LH and no FSH response, with variable PRL and TSH responses. The test was repeated after the patients received 100 micrograms GnRH im daily for 7 days. The LH, FSH, PRL, and TSH responses were similar to those obtained previously. The female patients were then retested twice, after priming with 17 beta-estradiol (2 mg daily for 7 days) and again after treatment with human menopausal gonadotropins. The male patients were treated with hCG and, after testosterone reached normal adult male values, the GnRH-TRH stimulation test was repeated. In both the female and male patients, the pituitary responses remained unchanged. These results demonstrate the presence of primary gonadotropin insufficiency as well as the lack of positive estrogen feedback mechanism in patients with thalassemia major. The site of this abnormality has been demonstrated to be the pituitary gland, since hemosiderosis of the pituitary without hypothalamic involvement has been found at autopsy in one patient.
Adult↗
Adrenocorticotropin-dependent virilizing paraovarian tumors in Nelson's syndrome.
A 35-yr-old woman with Nelson's syndrome presented with amenorrhea and virilization. Serum testosterone (T) concentration was 605 ng/dl and fell to 33 ng/dl when dexamethasone was administered. The MCR of T fell from 1383 to 991 liters/day and the T production rate decreased by 96%. With administration of synthetic ACTH, T concentration rose to 338 ng/dl. Plasma ACTH concentration paralleled T during repeated suppression testing, suggesting that T secretion was dependent on ACTH hypersecretion. Preoperative and intraoperative ovarian vein catheterization suggested that the predominant source of androgen production was from the right ovarian vein. Laporatomy revealed multiple paraovarian tumors in the right mesosalpinyx and mesovarium. Incubation of tumor slices and ovarian tissue with [3H]pregnenolone and [14C]17-hydroxyprogesterone demonstrated conversion of both precursors to T by the tumor and confirmed that the tumors were the source of androgen excess. The microscopic appearance of the tumors closely resembled the morphology of testicular and paratesticular tumors of men with congenital adrenal hyperplasia and Nelson's syndrome. The analogous dependency of the tumors on ACTH hypersecretion in men with paratesticular tumors and in this woman with paraovarian tumors suggests that the tumors may arise in both males and females from a common steroid-secreting cell of adrenogenital origin.
Adrenocorticotropic Hormone↗
Roles of estradiol and progesterone in eiliciting the midcycle luteinizing hormone and follicle-stimulating hormone surges.
The positive feedback effects of estradiol (E2) and progesterone (P) on LH and FSH release were studied under novel experimental conditions in three women of reproductive age who had undergone oophorectomy and received uninterupted E2 replacement by subdermal implants. Basal serum E2 levels were in the midfollicular phase range, while LH and FSH levels were normal or slightly elevated. Each volunteer underwent seven experiments at 2- to 4-week intervals, receiving im injections of increasing amounts of estradiol benzoate (E2B) alone and in combination with P. The time and dose of P (administered via P-impregnated polysiloxane intravaginal rings) were varied. In two of the seven experiments, P was given without E2B injections. In all three subjects, increasing serum E2 levels mimicking the preovulatory E2 peak were followed by a surge of LH but not of FSH. However, when serum P levels rose after an increase in serum E2 concentrations had occurred, the LH surge occurred earlier and was accompanied by an FSH peak. When serum P levels rose before serum E2 concentrations had risen or when P levels increased without a rise in serum E2, neither a serum LH nor FSH peak was observed. When administered concomitantly, E2B and P suppressed FSH but not LH levels, while P alone did not affect serum LH or FSH concentrations. These data indicate that an acute rise in serum E2 is a necessary condition for the midcycle LH and FSH surges, that P facilitates or blocks the positive feedback response of gonadotropin release in a time-dependent manner, and that P is required for the preovulatory FSH peak.
Adult↗