The hypothalamus and reproduction

The hypothalamus and reproduction

A Arimura

United States Department of Veterans Affairs

Abstract: This article has been designed to review recent developments in the field of hypothalamic hormones involved in the control of reproductive functions. A brief resume of early physiologic and anatomic studies was presented initially to give a better understanding of the concept of hypothalamic regulation of the release of gonadotropic hormones from the pituitary gland. Recently, an advance was achieved with the isolation from porcine hypothalami of a decapeptide which has both FSH-releasing hormone (FSH-RH) activity and LH-releasing hormone (LH-RH) activity. Its amino acid sequence was determined to be (pyro) gluhis-trp-ser-tyr-gly-leu-arg-pro-gly-NH2. The decapeptide corresponding to this structure was synthesized and shown to stimulate the release of LH and of FSH in laboratory and domestic animals and human beings. Natural and synthetic FSH-RH/LH-RH also stimulated the synthesis of both gonadotropins in tissue cultures of rat pituitaries in vitro. It was postulated that this decapeptide represents the hypothalamic hormone which regulates the release of both LH and FSH from the anterior pituitary gland. Complex effects of sex steroids on the release of LH and FSH were reviewed briefly. It was suggested that the over-all control of secretion of FSH and LH is most likely mediated by the interaction of hypothalamic FSHand LH-releasing hormone with sex steroids. Clinical studies performed with natural and synthetic LH-RH/FSH-RH were reviewed. These studies, particularly induction of ovulation, suggest that LH-RH should find practical application in the treatment of sterility. Subsequent synthesis of LH-RH/FSH-RH by several laboratories and drug houses should provide enough material for large-scale clinical evaluation of this hormone. Some comments were made concerning probable clinical use of LH-RH. Finally, some speculations were offered about the possibility of developing new birth control methods based on LH-RH/FSH-RH, its analogues, or its derivatives.


Stein-Leventhal syndrome

Stein-Leventhal syndrome

P de Paula e Silva

Escola Superior de Educação de Paula Frassinetti

American Journal of Obstetrics and Gynecology


Endocrine profiles in premenstrual tension

Abstract: Summary: Studies on pituitary and ovarian function as assessed by the urinary output of total gonadotrophic activity, the three classical oestrogens, pregnanediol and, in some cases, testosterone and epitestosterone, were conducted in eight patients suffering from premenstrual tension. Major abnormalities in endocrine function were not a feature of the condition. Ovulation, as judged by pregnanediol assays, was absent in seven out of the fifteen cycles investigated. Contrary to traditional belief, the symptoms of premenstrual tension could exist in the presence of cycles with anovulatory hormonal patterns.


The applicability of labor inhibition to the problem of prematurity


Outcome of pregnancy after induced ovulation. Follow-up of pregnancies and children born after clomiphene therapy

Abstract: Eighty-six women reached at least 20 weeks' pregnancy in 96 instances, after ovulation induced by clomiphene citrate. Although 37 of the women had 44 previous pregnancies, there had been a high pregnancy wastage (70.5%) producing only 13 live infants prior to the successful clomiphene therapy. After clomiphene therapy, pregnancies were normal except for a high incidence of toxemia (16.7%) and a possibly increased incidence of prediabetes. The pregnancies resulted in 88 single and 8 twin births. The total fetal and neonatal loss was 6.7%. The loss of single births (3.1%) included two stillbirth infants of prediabetic mothers. The twin loss of 25% was due to prematurity. The incidence of congenital malformations was within normal limits.


The effect of personal factors on the use of the basal body temperature method of  regulating births


Plasma estrone, estradiol, estriol, progesterone, and 17-hydroxyprogesterone in human pregnancy. I. Normal pregnancy

Abstract: To describe normal relationships between the various plasma unconjugated estrogens and progesterone during the second half of human pregnancy, the plasma concentrations of progesterone, 17-hydroxyprogesterone (17-OHP), and unconjugated estrone (E1), estradiol (E2), and estriol (E3) were measured in 126-310 normal women. Progesterone and unconjugated E1, E2, and E3 increased gradually throughout later pregnancy; 17-OHP increased only after the thirty-third week. At term the mean value of progesterone was 9 times higher than that 17-OHP. Throughout pregnancy the mean value of E2 was higher than that of E1 or E3. During the second half of pregnancy the ratios of progesterone to estradiol and estriol and of estradiol to estriol remained unchanged, indicating no preferential increase of plasma concentration of maternal or fetal hormones.


Single luteal phase serum progesterone assay as an indicator of ovulation

Abstract: A study was undertaken to determine whether solitary progesterone as says performed on serum samples obtained in the midluteal phase would provide the clinician with a convenient indicator that ovulation had occurred in that cycle. After a normal luteal-phase range was establish ed, single luteal-phase serum progesterone sampling was performed in 51 infertile women with regular menses and 35 oligomenorrheic women undergoing clomiphene citrate therapy. In the follicular phase of the cycle, progesterone levels were consistently less than 2 ng/ml. Between 11 and 4 days prior to the onset of menses in presumptively ovulatory cycles, serum progesterone levels were always 3 ng/ml or greater. Progesterone values in this range were always accompanied by a secretory endometrium and can be considered presumptive evidence of ovulation. This rapid, easily performed technique enables 1 technician to assay 30 or more samples for progesterone in a single working day and the results are available within 24 hours. This assay technique is easier to perform and more reproducible than a urinary pregnanediol assay, and it is expected that clinical laboratories will soon perform serum progesterone assays as a routine procedure.


The significance of the human corpus luteum in pregnancy maintenance. I. Preliminary studies

Abstract: Following the total removal of luteal tissue, circulating plasma progesterone, intrauterine pressure, oxytocin response, and clinical progress in abortion were determined sequentially in 12 first-trimester pregnant patients. 3 patients were ovariectomized for the removal of ovarian cysts and 9 were luteectomized during tubal ligation in an attempt to terminate pregnancy in spontaneous abortion. 7 patients had corpora lutea which averaged 21 plus or minus 1mm in diameter at operation when performed at Day 49 plus or minus 2 (mean S.E.) of pregnancy. These patients responded to ovariectomy or luteectomy by a continuing decrease in progesterone, evolution in intrauterine pressure, oxytocin response, progress in cervical dilitation and, abortion. Abortion occurred with a mean lapse time of 5 plus or minus 1 days after operation. In contrast, 5 patients whose corpora lutea averaged only 11 plus or minus 1mm in diameter when removed at Day 61 plus or minus 4 of pregnancy showed only transient decrease in progesterone after operation. This decrease was followed by an increase in progesterone; no progress in the evolution of intrauterine pressure, oxytocin response, cervical dilatation, and abortion. It appears that so long as the corpus luteum serves as the major source of progesterone, it is indispensable in the maintenance of pregnancy in human subjects as it is in the clinical model animal, the rabbit. However, with the shift of progesterone production from the corpus luteum to the placenta (the luteoplacental shift) the human corpus luteum becomes dispensable. These findings identify the corpus luteum and its secretory product, progesterone, as feasible targets of fertility control strategy.


Symptoms and hormonal changes accompanying ovulation


Cervical Mucus in Human Reproduction: Present State of Knowledge


Trends in Prematurity in the United States: 1950-1967


Luteal Phase Defects: Diagnosis and Implications

Thomas W Hilgers

Pope Paul VI Institute for the Study of Human Reproduction, Omaha, Nebraska.

xPharm: The Comprehensive Pharmacology Reference


Prostaglandin-induced myometrial activity inhibited by progesterone

Abstract: PROSTAGLANDINS (PGs) are being used increasingly as abortifacients although their precise mechanism of action is uncertain. One of the compounds frequently used is PGF2α, which has been shown to stimulate the myometrium in vitro1 and in vivo2. Whether or not the direct action of this agent on the uterine muscle alone is responsible for the interruption of pregnancy is not clear, but the long interval between infusion and abortion3 suggests that other mechanisms might be involved; for example, a luteolytic effect4–6. The prompt increase in uterine activity after treatment with prostaglandin, however, argues that the direct effect plays some part in the abortifacient action. Little is known of the influence of other myometrial regulatory agents such as the ovarian steroids on the uterine response to PGs. Accordingly we examined the influence of progesterone on myometrial responses to prostaglandin F2α in the rabbit, a species in which progesterone is known to have a blocking action on the uterine muscle7.


Stereospecific and nonspecific interactions of the morphine congener levorphanol in subcellular fractions of mouse brain

Abstract: A METHOD IS DESCRIBED FOR ANALYZING THE ASSOCIATION OF THE OPIATE NARCOTIC LEVORPHANOL WITH BRAIN TISSUE INTO THREE COMPONENTS: nonsaturable, saturable nonspecific, and saturable stereospecific. The method may be of general applicability for the study of the interaction of drugs with body tissues. In mouse brain the stereospecific binding of levorphanol represents only 2% of the total association of drug with tissue, and it was found only in certain membrane fractions. The material responsible for the stereospecific binding might be the opiate receptor.

Proceedings of the National Academy of Sciences of the United States of America


Use-effectiveness of oral and intrauterine contraception

Abstract: The use-effectiveness of oral contraception and intrauterine contraception was studied in 3 family planning centers in the United States: Grady Memorial Hospital in Atlanta, Georgia; State University of New York, Downstate Medical Center, in Brooklyn; and the Planned Parenthood Center in Buffalo, New York. In each locality 1000 women were selected for the study. 2900 women accepted intrauterine devices (IUDs) or oral contraceptives (OCs) as their first method of contraception. In Brooklyn 3 out of 4 women chose OCs; in Atlanta and Buffalo roughly equal numbers selected each method. The mean age of admission was 25.7 years in Buffalo, 24 years in Brooklyn, and 23.8 years in Atlanta. IUD acceptors were older than those choosing OCs. The difference was greatest in Buffalo (3.3 years) and smallest in Atlanta (.8 years). A special one-page, self-coding questionnaire was designed to collect the information required. In all 3 clinics contraceptive termination rates were markedly lower for the IUDs than for OCs. At 1 year of use for the first method only about one-fourth the women who chose the IUD had discontinued its use. Women on OCs terminated at rates from 10-20% higher. Termination rates for all contraception, both first-method and substitution, were lower than for first-method alone and lower for IUDs than for OCs. The highest continuation rate for all contraception was 92.5% for IUD users in Brooklyn while OC users in Atlanta were at the lowest level at 60.5%. Pregnancy rate studies demonstrated higher failure rates with OCs than with IUDs in all 3 clinics. Statistics by age showed that termination rates for both IUD and OC users declined with age. Women who selected IUDs as their method of contraception were more persistent users of contraception. Even after discontinuing IUD use, they were more likely to adopt another contraceptive method.


Peripheral plasma progesterone levels during human pregnancy and labor

E Knobil

Rotterdam University of Applied Sciences

American Journal of Obstetrics and Gynecology


Psychology of the misuse and rejection of contraception

Abstract: Some of the psychological influences on contraceptive misuse and rejection are presented, ranging from denial (of the possibility of pregnancy), guilt, sexual identity conflicts, to fear, opportunism (desperation) and iatrogenesis (influence of medical personnel. It is suggested that more attention be focused on these psychological factors as a means to successful population control rather than on the development of the "ideal" contraceptive. In discussion 4 doctors varied in their reactions to the authors' premise that social systems which require or allow volitional and individually initiated contraceptive use - as the sole method for population control - will fail to accomplish that goal.


The IUD and the pill: extended use-effectiveness

Abstract: The extended use-effectiveness of IUD and oral pills as measured by 1) their theoretical effectiveness 2) consistency of use and 3) continuation of use in preventing unwanted pregnancies was studied for 2900 women who had chosen either method as their first contraceptive in family planning clinics in Atlanta Georgia and in Brooklyn and Buffalo New York for a 12-18 month period. The greater persistence among IUD users to continue the method or use another method and the less likelihood there was of these women to have an unplanned pregnancy (the difference between IUD users and pill users increasing with months of exposure) suggest the necessity of greater support from the clinics to help women using pills prevent unwanted pregnancies. IUD users were generally older than pill acceptors and among IUD contraceptors the greater tendency to continue using the IUD and contraception may indicate that older women use contraception to terminate rather than to space childbirth.


Endocrine control of gestational length. A time to be born

American journal of obstetrics and gynecology


Nuclear magnetic resonance and cytometric studies on mucus from single cervical glands


Plasma levels of progesterone after vaginal, rectal, or intramuscular administration of progesterone

Baoyue Cui

College of Animal Science and Technology, Hebei Technology Innovation Center of Cattle and Sheep Embryo Hebei Agricultural University  Baoding Hebei China


Progesterone and 20 alpha-dihydroprogesterone in human myometrium during pregnancy


Experience with induction of ovulation

Experience with induction of ovulation

Abstract: One hundred and thirty-five patients diagnosed as ovulatory failure have been treated in our clinic since 1966. One hundred and eighteen of these have been treated with clomiphene citrate, or more recently, its cisisomer, and 17 patients with long-standing secondary amenorrhea or primary amenorrhea have been treated with human menopausal gonadotropins, in combination with human chorionic gonadotropins. Of the latter group, 14 of the 17 were shown to be capable of response to exogenous gonadotropins and 12 of these ovulated and 7 (50 per cent) became pregnant. The over-all ovulatory rate with clomiphene citrate or its cisisomer was 78 per cent, with a pregnancy rate of 31 per cent. The results of our present investigation with clomiphene citrate in 10 and 20 mg. dosage are presented in detail, and compared with our previous experience with clomiphene. It appears that cisclomiphene 20 mg. is as effective as clomiphene citrate 100 mg., but has the decided advantage of fewer side effects associated with its use. With the human menopausal gonadotrophins, no major complications, such as ovarian overstimulation or multiple pregnancies, were encountered, and we feel this is attributed to careful selection of patients and daily tracking of total urinary estrogens.


Plasma progesterone secretion by the corpus luteum of term pregnancy

Abstract: Plasma progesterone concentration was determined in the maternal peripheral vein, umbilical vein, uterine vein, and both ovarian veins at elective cesarean section in term pregnancy. In 10 cases plasma from both ovarian veins was analyzed. In all but one the ovarian vein draining blood from the corpus luteum contained greater concentrations of progesterone than did the blood from the side without the corpus luteum. It has been suggested for some time that the corpus luteum of pregnancy continues to function throughout pregnancy. Our data appear to support this concept.


Neonatal estrogen stimulation nd aggressive behavior in female mice


The short luteal phase

The short luteal phase

Abstract: From among a group of women with apparently normal menstrual cycles, 7 cycles with short luteal phases were identified. These cycles were characterized by grossly normal FSH and LH patterns although the FSH/LH ratio was below normal. Mean plasma progesterone increased to less than 2 ng/ml shortly after the LH peak; thus, the peak level was lower and the peak occurred earlier than in the normal cycle. Plasma 17-hydroxyprogesterone increased at the time of the LH peak although the mean peak level was only 60% that of normal cycles. There was no secondary increase of 17-hydroxyprogesterone during the luteal phase. These observations are consistent with the hypothesis that a relative deficiency of FSH during the follicular phase results in diminished follicular development and subsequent inadequate corpus luteum formation or function.

The Journal of Clinical Endocrinology and Metabolism


Psychologic aspects of the basal body temperature method of regulating births


Outcome of pregnancy after induced ovulation. Follow-up of pregnancies and children born after gonadotropin therapy


Plasma levels of progesterone in pregnancy measured by a rapid competitive protein binding technique

Abstract:
Plasma levels of progesterone* were measured during normal human pregnancy by a sensitive and rapid competitive protein binding technique. During the first half of gestation 440 determinations in 321 women and in the second half of gestation, 209 determinations in 160 women were performed.
The average plasma level of progesterone in the 5th week of gestation was 24.8 ± 7.3 (s) ng/ml which is above the normal range of the luteal plateau of the menstrual cycle (10–20 ng/ml). Between the 5th and the 9th week of gestation the plasma concentration decreased significantly. From the 9th to the 32nd week of gestation the plasma level of progesterone increased from 16.7 ± 7.4 (s) to 125.2 ± 37.9 (s) ng/ml. During the last 8 weeks of gestation the plasma levels of progesterone did not show any significant rise. One woman was followed up from the day of ovulation to the 8th week of gestation. An increase in progesterone levels was observed about 10 days after ovulation. Morning samples of progesterone, which were taken before the 20th week of gestation, when the woman was still in bed, were found to be somewhat higher than levels found during the remainder of the day.
Progesterone concentrations in a few abnormal pregnancies are also reported.


Evaluation of a new ovulatory stimulating agent: clomiphene citrate (clomid)

Abstract: Clomiphene citrate, in selected patients, is an effective agent for the treatment of infertility due to anovulation. An adequate laboratory and physical evaluation of each individual patient is essential for proper use of the drug. The major adverse reactions encountered are ovarian enlargements and cysts; in most patients, these conditions regress spontaneously after withdrawal of the drug.


Plasma progesterone levels in normal pregnancy, labor, and the puerperium. I. Method of assay

Abstract: A method to measure plasma progesterone by gas-liquid chromatography is presented. The procedure allows for the preparation of a plasma progesterone extract clean enough for accurate submicrogram quantification by gas-liquid chromatography. In a gas chromatograph equipped with a hydrogen flame detector, the instrument modifications and operating conditions as outlined make possible the measurement of 0.001 μg (1 ng.) of progesterone standard on a stable recorder base line. In biologic samples the sensitivity of the assay is in the order of 0.01 μg (10 ng.) of progesterone.

American Journal of Obstetrics and Gynecology


Plasma progesterone levels in normal pregnancy, labor, and the puerperium. II. Clinical data

Abstract: One hundred and seventy-two plasma progesterone determinations were performed in normal pregnancy, labor, and the puerperium. One hundred and nineteen of the assays were done on isolated samples; 53 of the assays were done in 11 serial studies. While the concentration of progresterone in peripheral blood increased progressively with advancing pregnancy, no apparent decrease in the hormone level occurred at or near the onset of labor or during its progress. A significant decrease in plasma progesterone one hour after the delivery of the placenta continued to decline to menstrual cycle levels by 72 hours post partum.


A field trial of the basal-body-temperature method of regulating births

Abstract: 502 couples used the basal-body-temperature method of regulating births through 8294 cycles. The overall failure-rate in those confining coitus to the postovulatory phase of the menstrual cycle was 6·6 pregnancies per 100 women-years, while in those having coitus in the preovulatory and postovulatory phases it was 19·3 pregnancies per 100 women-years. The biological effectiveness of the method was greater than this, and was achieved by certain subgroups in the survey.


Further clinical experience with clomiphene citrate


Statistical evaluation of contraceptive methods: Use-effectiveness and extended use-effectiveness

Abstract: The recent advent of national family planning programs and the expansion of local programs have created an acute need for accurate statistical evaluation of contraceptive methods. Effectiveness in terms of pregnancy rates and continuation or discontinuation of use of the contraceptive method or methods under study have emerged as the major criteria in such evaluations.


Pregnancy after clomiphene citrate treatment

Abstract:
For years the gynecological endocrinologist has been seeking an effective gonadotrophin for the treatment of ovarian dysfunction and anovulation in the human. 7
Animal preparations have been self-limiting because of allergic reactions, antihormone formation, failure to obtain a uniform response from a standard dose, and the absence of data on animal specificity.
A breakthrough occurred in 1958 when Gemzell et al. reported a human pituitary gonadotropin which induced follicular growth and estrogen production in the ovaries of amenorrheic women. The human source does not permit widespread application of this material. A few years later, Pergonal (HMG ),* a human menopausal urine gonadotropin which had similar effects,16 was developed; but standardization of HMG has been difficult and the extraction process complicated and expensive.
A most important contribution was made in 1959 by Tyler et al., who were able to induce ovulation in 6 patients with severe anovulatory problems, and in 1960 by Kistner and Smith, who successfully induced ovulation in 4 patients with the Stein-Leventhal syndrome, by using the estrogen antagonist MER 25.t Related compounds were further investigated and clomiphene citrate (Clomidt) proved more effective and had fewer side effects. 5, 12
The exact mechanism of action of the drug is stilI in doubt. It is postulated that clomiphene acts either directly on the hypothalamic-pituitary axis, causing an increase in gonadotropin output,9, 12, 17 or sensitizes the ovary to respond more readily to endogenous gonadotropins. 6
Smith and Kistner believe that Clomid directly influences the enzyme systems involved in ovarian steroidogenesis, or merely acts as a potentiator of gonadotropins. Pildes believes that there is a change in the synthesis of estrogen in both the adrenals and ovaries at the pre-estradiol phase of steroid synthesis.
Dickey et al. postulate a direct anti-estrogen effect in the system involved in estrogen metabolism, with subsequent stimulation of the hypothalamic-pituitary axis due to a fall in estrogen levels. Probably more than one mechanism of action is responsible for the response to the drug.
We first used clomiphene in the treatment of infertile patients with impaired ovarian function in May 1962. Because of the frequent side effects such as large ovarian cysts, reported by the early investigators, its use was limited to women with major endocrine defects and in cases where all other treatments had failed. With more experience and smaller dosages, 50-200 mg. daily for a short period of time, 3-5 days of each cycle, the drug was effective and most of the side effects were eliminated.14 With a program of at least monthly checkups, the drug proved safe and we have extended its use to infertile patients with only minor problems of ovarian dysfunction.
All patients, prior to treatment, have a thorough infertility and endocrine evaluation. The patient who is a proper candidate for this drug should be one with a moderately intact pituitary-ovarian axis and norm~or low total urinary gonadotropin levels, although we have had several patients with mildly elevated total gonadotropin who have responded. The patient should have a fair endogenous estrogen production. Thyroid function is usually normal or mildly subnormal. The 17-ketosteroid concentration is usually normal, although 32.5% of our patients who conceived did show levels of 13.0 mg. 24 hr. or more. Several of these decreased to normal levels after treatment with clomiphene; Pildes has reported a similar finding. Of our patients who conceived, 35.5% showed a diabetic or a prediabetic glucose tolerance curve on initial evaluation.
Pituitary tumors should be ruled out. Patients with ovarian damage due to chronic infection are not likely to respond. Since clomiphene citrate is detoxified in the liver, one should be hesitant to prescribe the drug to a patient with chronic liver disease.
Visualization of the ovaries by culpotomy with ovarian biopsy or culdos-copy is helpful in establishing the diagnosis, especially in patients who fail to respond.


Biophysical composition of cervical mucus and spermigration during treatment with Conluten and Conlunett

Acta obstetricia et gynecologica Scandinavica


The functional structure of human cervical mucus

Acta Obstetricia Et Gynecologica Scandinavica


Clomiphene citrate for improvement of ovarian function


Some aspects of the clinical communication of pain

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Journal of the American Medical Women's Association


Hormonal therapy for control of the incompetent os of pregnancy

Abstract: The concept that a cervix could be inadequate or incompetent for retaining a normal pregnancy was publicized by Lash and Lash in 1950. It did not catch the fancy of the majority of obstetricians to any extent until the introduction of the relatively simple corrective procedure advocated by Shirodkar in 1955 and publicized by Barter et al. Since then there has been a constantly increasing number of reports discussing this problem. Incompetent cervical os is estimated to represent only a small percentage of all causes of fetal wastage …


An instrument for transcervical treatment of the oviducts and uterine cornua

Abstract: A new instrument has been designed to treat the primate uterine cornua and oviducts. 2 versions of the instrument are described. Both versions are 12 cm long. One is 3 mm in diameter, and the other is 3.5 mm. Tips may be manufactured to hold different volumes of fluid. The Teflon piston which is moved inside the tip, forces the fluid out through a small hole at the end. The piston is actuated from the proximal (operator's) end of the strument. Silicon rubber tubing may be filled with air or fluid from the stopcock at the operator's end through a fine tube which runs inside the instrument. In an attempt to determine if the instrument will locate fluids reliably and accurately, a vital stain, cresyl violet, has been used to inject normal sized uteruses in 6 patients prior to operation for various conditions. In 3 patients, both cornua were successfully stained with dye. In 2 patients, the cornu on only 1 side was seen to be stained, and in 1 patient, no stained areas were identified. Suggested applications of the instrument include: 1) investigation of oviduct physiology; 2) temporary sterilization; and 3) permanent sterilization.


Prevention of postoperative intestinal adhesions with combined promethazine and dexamethasone therapy: experimental and clinical studies

Abstract: This study, combining experimental and clinical data, attempted to develop methods to prevent formation of adhesions in the highly susceptible infant undergoing abdominal surgery and to inhibit reformation of adhesions after surgical division of those which had appeared after some previous operation. Rats were treated with a combination of dexamethasone (Decadron) and promethazine (Phenergan). This series showed that the inflamma tory phase that follows trauma to intestinal serosa can be minimized and the organization of inflammatory exudate into fibrous adhesions can be delayed with this combination treatment (antihistamine plus adrenal cortex hormones). An addendum notes that so far 81 patients have been treated with the drug combination, and the results are characterized as very satisfactory, with no complications related to treatment. 2 points are emphasized: 1) since adhesion formation begins within minutes of peritoneal trauma, prevention requires a high level of drug saturation at the time of injury; and 2) large doses of drugs are required for maximum benefit. Experimentally, this study used 1 mg/kg of each drug, intramuscularly, 6-3 hours preoperatively, with dose repetetion via intraperitoneal saline as the abdomen is being closed for 2-36 hours postoperatively.


Habitual Abortion Treated with 17 Alpha-Hydroxyprogesterone Caproate


Reconstructive tubal surgery

Reconstructive tubal surgery


Double-Dash Blind Controlled Trial of 6-Methyl, 17-Acetoxyprogesterone in Threatened Abortion


Hormones in Recurrent Abortion

Hormones in Recurrent Abortion

BJOG: An International Journal of Obstetrics & Gynaecology


FURTHER OBSERVATIONS ON THE EFFECTS OF CLOMIPHENE CITRATE IN ANOVULATORY FEMALES

American Journal of Obstetrics and Gynecology


The clinical use of clomiphene citrate

The clinical use of clomiphene citrate


Clomiphene citrate: Its uses and observations on its probable action


CLOMIPHENE CITRATE IN THE MANAGEMENT OF ANOVULATORY UTERINE BLEEDING

Abstract: Clomiphene citrate [1-p(β-diethylaminoethoxy) phenyl-1,2-diphenyl-2-chloroethylene citrate], because of its ability to induce ovulation, was administered to 26 patients with excessive anovulatory uterine bleeding. Of the 129 menstrual cycles during which the drug was administered, 105 cycles (81.3%) were ovulatory and were followed by normal uterine bleeding. After clomiphene was discontinued, observations made in 52 cycles showed that only 20 (38.4%) were ovulatory

The Journal of Clinical Endocrinology and Metabolism


ACTION OF PROGESTERONE AS A CLEAVAGE INHIBITOR OF RABBIT OVA IN VITRO

Abstract: Summary. The manner whereby progesterone acts as an inhibitor of cleavage of mammalian ova was studied using rabbit ova in vitro. Progesterone blocked cleavage when it was present in the culture medium at concentrations of 10 µg/ml more, and exerted this same effect on all stages up to the morula. The growth of blastocysts was not affected. The action was reversible: ova resumed cleavage within 2 to 3 hr after removal to progesterone-free media. The reversal was time-specific and was used to phase the subsequent cleavage of ova inhibited for varying periods of time. The inhibition was overcome by increasing the concentrations of amino acids or of the serum component in the medium. Supplementing the progesterone media with oestradiol did not reverse the inhibition. Autoradiographs of sections of ova that were kept in C-labelled progesterone for 8 hr, showed silver grains concentrated on the surface of the ovum and the zona pellucida. It is concluded that progesterone blocks cleavage by limiting the supply of protein or amino acids and thus inhibiting protein synthesis within the ovum. Presumably this is done by the progesterone aggregating on the surface of the cell or its protective coating. The inhibitory action appears to be timed in relation to some event that precedes mitosis by an hour or two. It is therefore suggested that the protein synthesis involved is related to formation of the mitotic apparatus or to chromosome condensation.


THE EFFECT OF PROVERA ON THE FETUS

THE EFFECT OF PROVERA ON THE FETUS

Abstract: 239 women received medroxyprogesterone during their pregnancies; they received no other hormone therapy. Of the 203 who went to term 172 were treated prior to the 12th week; the latter are discussed. Average daily dose varied from 5-50 mg or more orally with or without injectable supplements. Sex distribution of infants was 92 male to 82 female there were 2 sets of twins 1 stillborn and 1 newborn with congenital heart disease. The authors report a case of transient masculization of a female infant born with an enlarged clitoris which persisted until age 6 months. Masculization of the female fetus may occur if the fetus is subjected to some source of androgen prior to the 12th week of gestation after which the female generative tract is well differentiated and not likely to be affected. Other studies have reported up to 18% masculization using exogenous hormones with abnormalities as extreme as labial fusion and cloacal formation necessitating surgical correction.


DOUBLE-BLIND TRIAL OF A PROGESTIN IN HABITUAL ABORTION

Abstract: Study of 54 habitual aborters with low or normal pregnanediol excretion, in a double-blind trial, revealed the spontaneous-salvage rate and the possible benefit of therapy with medroxyprogesterone acetate. The salvage rate in the placebo group with the worst prognosis (never a term pregnancy, low pregnanediol in the current pregnancy) was ten of 13, and the salvage rate in the other placebo groups showed no statistically significant difference. In view of this high spontaneous salvage rate, the numbers required to demonstrate a therapeutic effect of progestin administration are prohibitively large. This indicates the need for new criteria to pinpoint cases with a poor prognosis, and it raises the question whether habitual abortion is a disease entity or a statistical coincidence.


INDUCTION OF OVULATION WITH CLOMIPHENE CITRATE


Spontaneous Abortion Risks in Man: Data from Reproductive Histories Collected in a Medical Genetics Unit

Abstract: SPONTANEOUS ABORTION is one of the most common and least understood pathological processes. Because it is so difficult to obtain reliable information about abortion, even the basic facts about its frequency, familial distribution, and relation to parity and parental age are largely unknown or disputable. Such information is needed to provide a basis for advising women with several abortions about their chances of successfully completing another pregnancy, to evaluate measures for the prevention of abortion, as well as to provide clues to the etiology of the condition. Reproductive histories taken by personal interview with a random series of women would probably be the best available data for estimating spontaneous abortion statistics. These would include very early terminations of pregnancy, recognized as spontaneous abortions by the women concerned but not receiving medical attention, which are under-represented in series of consecutive hospital admissions or in consecutive cases from private obstetrical practice. They would allow estimation of abortion risks in women with given numbers of previous abortions and at given ages. Some reservations must be held about the validity of self-diagnosis of early abortion, but this source of error should not affect comparisons within the sample.


PURIFICATION OF GONADOTROPHIN FROM HUMAN MENOPAUSAL URINE

Abstract:
Gonadotrophins were prepared from human postmenopausal urine with the kaolin-acetone method and purified by adsorption of impurities on diethylamine ethyl cellulose (DEAE-C).
The last step, namely chromatography on the column of permutit, resulted in a significantly improved specific activity.
The immunoelectrophoresis showed that the purified HMG is not homogeneous and that the constituents are glycoproteins which migrate into the region α1, α2and β globulins.


LIPOTROPIN, A NEW ACTIVE PEPTIDE FROM PITUITARY GLANDS


Duration of fertility following ovarian wedge resection--Stein-Leventhal syndrome

Western Journal of Surgery, Obstetrics, and Gynecology


DETERMINATION OF PLASMA PROGESTERONE DURING PREGNANCY

Abstract: A modification of Short's method for the determination of plasma progesterone is described, which allows the estimation of 0.5–1.0 μg per sample. The reliability of the method is tested and plasma levels in cord and peripheral blood during pregnancy are reported.

Clinica Chimica Acta; International Journal of Clinical Chemistry


CLOMIPHENE CITRATE: FURTHER OBSERVATIONS ON ITS USE IN INDUCTION OF OVULATION IN THE HUMAN AND ON ITS MODE OF ACTION

Abstract: Induction of ovulation in the human has been of considerable research interest for several decades. Various hormonal regimens and other procedures have been tried in the past.1 • 2 In spite of all these trials, the problem of ovulatory failure remains a frustrating dilemma for the physician. Recently, the induction of ovulation with clomiphene citrate in about 70% of anovulatory women was reported by our group.3- 6 It was felt that an important breakthrough in this difficult field of endeavor was at hand. 7- 9 Our observations have been confirmed by other groups of investigators.10- 12 The present report embodies a detailed analysis of the results of administration of this agent to 200 women, of whom 179 were anovulatory. The results of our studies on the probable mode of action of this drug are also discussed.


Action of MER-25 and of clomiphene on the human ovary

Abstract: IT APPEARS TO BE WELL ESTABLISHED that the synthetic nonsteroidal analogue of chlorotrianisene (Tace), which has been given the generic name of clomiphene citrate (MRL/41)*, is capable of stimulating ovarian secretory activity in women.1-4 Perhaps the most convincing evidence for this is found in the high incidence of cystic ovaries observed among treated patients, together with the associated microscopic ovarian and endometrial changes, indicating that the cystic structures produced are functional.2,3 The striking similarity between the histopathology of this response to clomiphene and the ovarian response to administered gonadotropins of both human and animal origin has been pointed out by Southam and Janovski.2 With both forms of treatment, the degree of ovarian response to a given dosage appears to be unpredictable and all patterns of atypical stimulation have been observed. In view of this analogy, it has been logical to assume that the ovarian response


Double-blind study of effect of 17-hydroxyprogesterone caproate on abortion rate

Abstract: After many years of use and a large number of publications there is still no good evidence to indicate that progestogens have a valid role in the treatment of patients with a history of abortion. In many of the published series the amount of material administered has been inadequate in the light of current concepts of progesterone secretion in pregnancy (Zander, 1959) and inadequate control observations have invalidated much published data. To assess the salvage rate in treated pregnancies and then compare it with that found for previous untreated pregnancies in the same patients ignores the number of pregnancies that would have reached viability if no treatment had been given at all. Malpas (1938) produced a theoretical estimate that any woman with a history of three consecutive abortions. . .


[PHYSIOLOGY AND PATHOLOGY OF CERVICAL MUCUS. II. PATHOLOGY]


[PHYSIOLOGY AND PATHOLOGY OF CERVICAL MUCUS]


In vitro inhibitory effect of progesterone on extrauterine human smooth muscle

American Journal of Obstetrics and Gynecology


Plasma progesterone in mother and foetus in the second half of human pregnancy

The Journal of Obstetrics and Gynaecology of the British Empire


Induction of ovulation

Induction of ovulation

American journal of obstetrics and gynecology


Comparison of the acetophenone derivative 16alpha,17alpha-dihydroxyprogesterone with other progestational steroids for masculinization of the ratfetus

Abstract: A new progestational steroid, the acetophenone derivative of 16α,17α;- dihydroxyprogesterone, was compared with several progestogens for masculinizing effects on the offspring of rats treated during pregnancy. The results were similar to those obtained with progesterone and 17α-hydroxyprogesterone caproate: this new steroid did not alter the normal male:female sex ratio and did not virilize the internal or external sex structures of the newborn. The present results confirm those of others in finding that 6α-methyl-17α-hydroxyprogesterone acetate, 17α-ethinyl-19-nortestosterone and 17aethinyl- 19-nortestosterone acetate increased the number of male and intersex offspring, as determined by ano-genital measurements and masculinization of internal and external sex organs.


M.R.L.41 in the treatment of secondary amenorrhoea and endometrial hyperplasia


Blood-progesterone and urinary pregnanediol and oestrogens in foetal death from severe pre-eclampsia


Controlled trials in the prophylactic value of progesterone in the treatment of pre-eclamptic toxaemia


Undulations of macromolecules in cervical mucus


Lunenfeld B, Sulimovizi S, Rabau E, et al: Compt Rend Soc Franc Gynecol 35:346, 1962

Comptes rendus de la Société Française de Gynécologie


The Excretion of Œstriol and Pregnanediol in Toxæmia of Pregnancy and in Postmaturity

Acta Obstetricia et Gynecologica Scandinavica


Induction of Ovulation with MRL/41

Induction of Ovulation with MRL/41


Chemical induction of ovulation

Chemical induction of ovulation


The catabolic and natriuretic effects of progesterone in man


The Merck Index of Chemicals and Drugs: An Encyclopedia for Chemists, Pharmacists, Physicians and Members of Allied Professions


Monthly rhythm of libido in married women

Abstract: Since classical times there has been discussion on the existence or non-existence of variations in libido in women during the menstrual cycle.*This discussion reached its peak in the nineteenth and early part of the present century.The main difference of opinion lay between those who believed that there was increased libido in association with menstruation itself-that is, just before, just after, or during, or various combinations thereof (for example, Campbell, 1891 ; Kossmann, 1903; Havelock Ellis, 1910)-and those who denied the existence of any monthly enhancement of sexual desire in women (for example, Ftirbringer, 1918).The more recent literature continues to show marked differences of opinion.Thus Corner (1952) maintained that libido is maximal just before or just after menstruation, whereas Stopes (1937) considered the monthly rhythm to have two peaks, one just before menstruation and the other at mid-cycle.On the other hand, Eckstein and Zuckerman (1956) stated that " sexual behaviour in women very rarely manifests any rhythmic pattern."However, according to Swyer (1954), " Psychic changes occur throughout the menstrual cycle.So great are the variations in different individuals that generalizations are difficult to draw.Thus, whereas some women lose all or most of their libido during the menstrual period,


The place of progesterone in the treatment of abortion


The pregnanediol excretion in suspected placental insufficiency


Hypotensive action of progesterone in experimental and human hypertension

Abstract: Summary(1) Progesterone administration to rats and dogs with experimental hypertension and to humans with primary arterial hypertension resulted in a decline in blood pressure levels. Blood pressures increased once more in all cases after progesterone was discontinued. (2) In humans, but not necessarily in rats and dogs, blood pressure reduction would appear to have resulted from natruresis.

Proceedings of the Society for Experimental Biology and Medicine. Society for  Experimental Biology and Medicine (New York, N.Y.)


The clinical effectiveness of contraceptive methods

Abstract: Physiologic effectiveness is the measure of protection against unwanted pregnancy afforded by a specific contraceptive method under ideal conditions ie, used consistently and according to instructions-without omissions, or errors of technique. Such ideal conditions are rarely present. Even when they are, it is not practicable to observe and verify them. Physiologic effectiveness, although not accessible to direct measurement, is by definition higher than the observed clinical effectiveness of the same method in the hands of the most …

American Journal of Obstetrics and Gynecology


Progesterone in blood. III. Progesterone in the peripheral blood of pregnant women

Abstract: Summary: The content of progesterone was determined in the peripheral venous blood of pregnant women from the 11th week after the last menstrual period up to the day of birth. There was a steady increase in the blood level from the 11th to the 35th week, but thereafter the level rose more rapidly, and remained high during labour itself. The significance of this rise after the 35th week is not fully understood. It may reflect a decrease in the rate of progesterone metabolism which occurs at this time. The blood level in three cases of twin pregnancy tended to be higher than the corresponding levels for single pregnancies. After removal of the placenta during elective caesarean sections, it was found that the blood progesterone level rapidly fell below the limits of sensitivity of the method. It has been estimated that the half-life of progesterone in the circulating blood must be 5 min or less.


Some aspects of the urinary excretion of pregnanediol in pregnancy

Abstract: Results: Normal Pregnancy. Eleven pregnant women were studied at weekly intervals for periods ranging from 24 to 32 weeks. Three hundred and ten estimations were done in this group. An additional 68 assays were made in 40 patients at various stages of pregnancy, a total of 378 estimations being done in 51 patients, 189 in primigravidae and an equal number in multigravidae. Two of the patients in the first group had been attending the sterility clinic before becoming pregnant. None of the patients were suffering from hypertension …

The Journal of Obstetrics and Gynaecology of the British Empire


Clinical effect of human pituitary follicle-stimulating hormone (FSH)

Abstract: A partially purified follicle-stimulating hormone preparation (human pituitary FSH) has been obtained from human pituitaries. The ovarian response to this preparation was studied in 7 amenorrheic women. The effect of human chorionic gonadotropin (HCG) was studied in addition. In 4 patients exhibiting no endometrial activity or only slight proliferation, HCG alone did not induce ovulation and had no effect on the size of the uterus, on the endometrium, or on the urinary excretion of estrogen and pregnanediol. In 2 patients showing endometrial proliferation, the administration of HCG alone was followed by ovulation, a secretory transformation of the endometrium, and a marked increase in urinary pregnanediol excretion. The administration of human pituitary FSH alone to 2 patients resulted in an increase in the size of the uterine cavity, in polycystic enlargement of the ovaries, and in a pronounced increase in urinary estrogen output. Treatment with human pituitary FSH followed by HCG produced in all patients polycystic enlargement of the ovaries, ovulation in 4 out of 5, and a secretory transformation of the endometrium in 3 out of these 5 patients. Ovulation was accompanied by a marked increase in the urinary excretion of both estrogen and pregnanediol.

The Journal of Clinical Endocrinology and Metabolism


Masculinization of the female fetus associated with administration of oral and intramuscular progestins during gestation: non-adrenal female pseudohermaphrodism

Abstract: There are relatively few reports of female pseudohermaphrodism not associated with congenital adrenal hyperplasia. The writers report 21 cases of females born with partial masculinization of the external gcnitalia, consisting of an enlarged phallus, with or without varying degrees of fusion of the labioscrotal folds. The diagnosis was established by finding female chromatin patterns, low excretion of urinary 17-kctosteroids and absence of progressive virilization. Exploratory laparotomy revealed normal ovaries and a normal female genital tract, although in some cases the vagina and urethra opened into a common urogenital sinus. In 15 of the cases, the mother had been treated because of threatened or habitual abortion with an oral progestin, 17-cthinyltestosterone (anhydrohydroxyprogesterone or ethisterone), marketed undersuch trade names as Pranone, Progestoral and Lutocjlol. In 2 cases the mother had received intramuscular injections of progesterone. In 1 case both intramuscular progesterone and oral methyltcstosterone had been given. In 3 cases no steroids were administered during pregnancy. The progestinic medication was usually begun before the tenth week of gestation and in most instances between the fourth and sixth weeks. Reasons are discussed for believing that the oral and intramuscular administration of progestins induced the partial masculinization of the female fetus. It is believed that the female fetus is affected in only occasional mothers who receive these steroids, and that in such mothers there may be an abnormality of cither the metabolism of progestins or their transmission across the placenta. It is most important to diagnose the condition correctly at birth, and to rear the infant as a female. No treatment is required except surgical correction of the abnormalities of the external genitalia. Normal female development is certain.


Nonparametric Estimation from Incomplete Observations

E. L. Kaplan

University of California Radiation Laboratory

Abstract: Journal Article Pus collections in hernial sacs. An unusual complication of general peritonitis Get access K Cronin, K Cronin Department of Surgery, Radcliffe Infirmary, Oxford Search for other works by this author on: Oxford Academic Google Scholar H Ellis H Ellis Department of Surgery, Radcliffe Infirmary, Oxford Search for other works by this author on: Oxford Academic Google Scholar British Journal of Surgery, Volume 46, Issue 198, January 1959, Pages 364–367, https://doi.org/10.1002/bjs.18004619810 Published: 06 December 2005

Journal of the American Statistical Association


The effect of progesterone on the development of mouse eggs in vitro

Abstract: SUMMARY 1. The action of progesterone on the development of the mouse ovum from the eight-celled stage to the blastula has been studied in vitro . 2. Concentrations of progesterone below 2 μg/ml. produced no observable effect, whereas some toxicity was observed at 4 μg/ml. and few ova survived higher concentrations. 3. Herniation of the zona pellucida by the developing blastula is described; this process was inhibited by 4 μg/ml., but not by 2 μg/ml. of progesterone. 4. Blastulae appear to be more sensitive to the action of progesterone than are earlier stages. 5. Oestrogens afforded no demonstrable protection against the toxic action of progesterone when added to the culture medium. 6. The possible physiological significance of these findings is discussed.


Pregnanediol excretion in normal and abnormal pregnancy


Toxaemia of pregnancy treated with progesterone during the symptomatic stage

Abstract:
While investigating the use of progesterone for the relief of premenstrual syndrome (Greene and Dalton, 1953) a high incidence of toxaemia of pregnancy (19.1 %) was recognized among sufferers from this syndrome. A further investigation, undertaken to ascertain the incidence of premenstrual syndrome in those who had previously suffered from toxemia of pregnancy, revealed that 86% of the 237 women thus affected at one time or another during the previous twelve years also suffered from premenstrual syndrome (Dalton, 1954). Furthermore, direct questioning and a scrutiny of records of these patients showed that before the full development of the signs of toxaemia–that is, oedema, hypertension, and albuminuria–most had earlier in the pregnancy experienced a symptomatic stage characterized by relatively minor afflictions–for example, lethargy 43 %, headache 48%, visual aura 37%, vertigo 29%, nausea and vomiting 16%, irritability 14%, depression 9%, and backache 6%. In fact, only 7% disclosed freedom from these symptoms during a toxaemic pregnancy. Of the 237 women, 92 (38.8%) had experienced both a normal and a toxaemic pregnancy, and 72 (78 %) contrasted the sense of well-being associated with a normal pregnancy with the malaise and minor symptoms characteristic of the toxaemic condition.

The striking feature of these early minor symptoms of toxaemia was their close resemblance to those of premenstrual syndrome noted in an earlier investigation (Greene and Dalton, 1953), most patients confirming that the minor symptoms during their toxaemic pregnancy were similar, though of increased severity, to those experienced in the premenstruum, irrespective of whether the onset of premenstrual syndrome had preceded or followed the toxaemic pregnancy.

Apart from the similarities of these minor symptoms in the two conditions, other points in common were noted.

For example, day-to-day observations of sufferers of premenstrual syndrome had shown that, apart from minor symptoms, some developed oedema, hypertension, and albuminuria during the premenstruum, with spontaneous improvement during menstruation.

This appeared to be analogous to the spontaneous resolution of oedema, hypertension, and albuminuria following delivery. Furthermore, if symptoms remain untreated either in premenstrual syndrome or in toxaemia both diseases may culminate in fits, epileptic in the one case, eclamptic in the other.

In an earlier investigation one of the reasons for using progesterone in the treatment of premenstrual syndrome had been that some patients suffering from this condition were symptom-free during pregnancy. It was considered that the corpus luteum and placenta supplied enough progesterone during pregnancy to keep these patients symptom-free. Others were not only unrelieved of their premenstrual symptoms during pregnancy, but, as already indicated, developed symptoms closely resembling those of the premenstruum and culminating in toxaemia. It was therefore thought possible that the development of toxaemia might in such cases arise from failure of the corpus luteum and placenta to produce sufficient progesterone.

In the light of similarities between premenstrual syndrome and toxaemia, and the fact that treatment of the former with progesterone not only relieved the symptoms (Greene and Dalton, 1953) but also prevented the development of edema, hypertension, and albuminuria in the premenstruum (Dalton, 1954, 1955), it was decided to carry out a trial, employing large doses of progesterone in patients disclosing early minor symptoms of toxaemia, in an attempt to arrest full development of that condition.


Progesterone block

Progesterone block

Abstract: In 1899 Gustav Born advanced the theory that the corpus luteum of the ovary is a gland of internal secretion, its activity being a prerequisite for the implantation and early development of the fertilized ovum. Conclusive proof of the theory was provided by Fraenkel ('10) in demonstrating that cauterization of the corpora lutea in pregnant rabbits leads to the resorption of the fertilized ova, provided that the operation took place during the first 7 days of gestation. He extended the period of the indispensable role of the corpora lutea in the …


Inhibition of the release of pituitary ovulatory hormone in the rat by morphine

Abstract:
AMENORRHEA and sterility are frequent accompaniments of morphine addiction in the human female (Menninger-Lerchenthal, 1934; Pescor, 1938). The mechanisms by which these effects are induced, however, are not clearly understood. In experimental animals results are contradictory. Myers and Flynn (1928, 1931) failed to observe any disturbance of estrous cycles, ovulation or fertility despite 132 days of chronic morphine treatment in rats, and their results were confirmed by Forster (1928). In contrast, treatment of mice daily for a two-month period with morphine has been reported to suppress estrus and induce atrophy of the ovary and uterus (Ko, 1934). Similar observations were noted in the rabbit (Bun, 1937).
The finding by Everett and Sawyer (1950) that “spontaneous” ovulation in the rat involves a neurogenic timing factor with a 24-hour rhythmicity offers a new approach to the study of the control of ovulation.


Progesterone in human blood and tissues

Progesterone in human blood and tissues

Abstract: THE problem as to whether progesterone is present in human peripheral blood, and in what concentrations, has not yet been solved satisfactorily.


Study of the inadequate secretion phase endometrium


Cervical mucus arborization; its use in the determination of corpus luteum function


Progesterone implantation in habitual abortion


Spinnbarkeit: a characteristic of cervical mucus; significance at ovulation time

Abstract:
Accurate timing of ovulation is especially necessary (1) in artificial insemination in order to avoid wastage of donor semen; (2) in cases where the husband is relatively infertile and it is necessary to conserve his semen. While many physicians rely upon the basal body temperature curve for timing ovulation, the interpretation of such curves is varied. Some physicians believe ovulation occurs prior to the lowest point in the temperature cycle, while others believe that ovulation occurs either at the low point or following the thermal shift. We have been disappointed in our ability to interpret the basal body temperature curve for accurate timing of ovulation, and have placed greater reliance upon concurrent phenomena, such as changes in the quantity and viscosity of cervical mucus and the cyclic changes observed in the vaginal smear. Although the relationship between the occurrence of a profuse, thin cervical mucus discharge and the optimal time of fertility in the human has been recognized for the past century, in our opinion this relationship requires further evaluation.
In his excellent review, "Cervical mucus: Cyclic variations and their clinical significance," Shettles quotes Robin who, in 1848, noted the viscous nature of human cervical secretions; and Smith who, in 1865, concluded that conception is most likely when the mucus contents of the cervix are in the most fluid condition. J. Marion Sims, who invented a vaginal speculum and first described the postcoital examination in 1868, observed that the test is positive for motile spermatozoa when the cervical mucus becomes clear and translucent, and about the consistency of the white of egg. Although these observations on human cervical mucus have been well documented, they have been almost disregarded by gynecologists. The significance of the cyclical outpouring of cervical mucus has been rediscovered in the past few years and has aroused great interest in students of sterility.
The optimal time of fertility in domestic animals is the period of heat or estrus. In 1925, Woodman and Hammond showed that during estrus, bovine cervical mucus is fluid and capable of being drawn out into threads, whereas in diestrus the mucus is thick. Seguy and Vimeux, and Seguy and Simonnet called attention to the optimal conditions of longevity of human spermatozoa in the fluid, glairy mucus of the cervix at midcycle. They postulated that these changes in cervical mucus were associated with ovulation and could be compared to the period of estrus in subprimate mammals. They correlated these changes with visual evidence of ovulation at laparotomy.

Subject: ively, many women observe an increased sticky, mucoid discharge which is typical at midcycle and which is present over a period of days. On occasion this discharge is blood-tinged and may be compared to the distinct bloody mucoid discharge present in the domestic animal "in heat."
This mucus can be seen exuding from the cervix at midcycle and it may be aspirated from the endocervix and actually weighed, as reported by Viergiver and Pommerenke. Clift demonstrated certain rheologic properties of cervical mucus, especially flow elasticity and Spinnbarkeit. Flow elasticity, or elastic recoil of mucus, is measured by an instrument described by Blair. The use of the Blair capillary viscometer is a cumbersome method which we discontinued. We have had no experience with the new modification of the viscometer described by Clift, Glover, and Blair. Spinnbarkeit is easily tested, and we have found it to be a very practical objective method for determining viscosity of cervical mucus. In performing this test (Fig. 1), a vaginal speculum is inserted, exposing the cervix. A glass cannula is inserted into the endocervix and by means of gentle suction, a quantity of endocervical mucus is obtained. This mucus is blown onto a glass slide and a cover slip is placed on it. The mucus adheres to both the slide and the cover slip, and by withdrawing the cover slip, a thread of mucus is formed which can be measured in centimeters (Fig. 2). Usually, the cover slip is withdrawn several times, and the average length of the thread is ascertained. It is our purpose to show the relationship of Spinnbarkeit to other cyclic phenomena occurring during the menstrual cycle, such as basal body temperatures, vaginal smears, quantity of cervical mucus, and longevity of spermatozoa (Fig. 3).


A simple test for the determination of ovulation, estrogen activity, and early pregnancy using the cervical mucus secretion; a preliminary report

American Journal of Obstetrics and Gynecology


Pregnanediol determinations in the clinic and in research

Abstract: PREGNANEDIOL was first isolated by Marrian (1) in 1929, when he was engaged in thepurification of “oestrin” from pregnancy urine. He described the properties of this new “unidentified solid alcohol” very precisely, and his first analyses came surprisingly near to the right formula, C21H36O2,at a time when the greater part of steroid chemistry was still unknown. To-day, looking back on twenty years of chemical, biologic, and clinical research, it is comparatively easy to see the principal features of the interesting pattern which centers around the pregnanediol molecule. The first clue to the biologic significance of pregnanediol is given by its structural formula which shows a striking resemblance to that of the corpus luteum hormone, progesterone. Pregnanediol is nothing else but reduced progesterone, with all the double bonds of the latter saturated by hydrogen. Thus, the obvious inference would be that urinary pregnanediol is a metabolite of progesterone. This important fact is the reason why so many workers are interested in pregnanediol determinations.


A 24-hour periodicity in the "LH-release apparatus" of female rats, disclosed by barbiturate sedation


Habitual abortion; prophylactic value of progesterone pellet implantation

Abstract: BRLTISH MDCLJOURNA physical disease: in no case referred for psychological reasons was the mental factor regarded as strong enough for interruption of the pregnancy.


Time required for conception in 1727 planned pregnancies


Ovarian resection for the relief of sterility

Abstract:
More than twenty-five years ago Edward Reynolds gave an excellent description of the polycystic ovary, and expressed the opinion that ovarian surgery was the most important single feature in the treatment of sterility of the female. This view was not accepted by later workers in the field. Indeed, the tendency has been to consider retention cysts as items of small importance, unlikely to cause symptoms and rarely calling for treatment on their own account. It remained for Stein15- 18 and his followers to define a type of case where the presence of multiple cysts evidently interferes both with ovulation and with endocrine activity, and to show that surgery frequently succeeds in restoring normal function. I propose to discuss certain aspects of this clinical problem, and to report my own series of 65 operated cases.
The fundamental cause of retention cysts is probably, as Zondek believes, a phase of hypergonadotropism. Under normal conditions large numbers of primordial follicles start to mature but never complete the process. At some point along the way the ova die, whereupon the follicles regress and ultimately become insignificant corpora fibrosa. Under the influence of excessive pituitary stimulation, however, such follicles may continue to secrete liquor and to grow after the disappearance of their ova.
Some of them eliminate themselves by delayed resorption and atrophy or, less often, by rupturing through the tunica albuginea. Others remain as permanent cystic structures. These retention cysts are pathologic, whereas atretic follicles in various stages of regression represent nothing more than phases of the normal ovulatory cycle.


The Thermogenic Property of Progesterone


80. Hydroaromatic steroid hormones. Part I. 10-Nortestosterone

Abstract: A. J. Birch, J. Chem. Soc., 1950, 367 Doi: 10.1039/JR9500000367

Journal of the Chemical Society (Resumed)


Some newer aspects of the management of infertility

Abstract: A discussion of infertility would be incomplete without a comment on the changing concepts of the definition. For statistical purposes it may be necessary to retain the criterion of a three year barren marriage. However, for the most satisfactory therapeutic results it appears that investigations for infertility must be instituted before these three, possibly most valuable, years have been wasted. The validity of shortening the period is substantiated by work of Diddle1 and Guttmacher,2 who independently obtained a figure of six months as the average time for a normal couple to achieve pregnancy. Relative infertility may be considered to exist any time after a six month interval. As late marriages and prolonged use of contraceptives are an integral part of our present society (especially in the private practice group) the foregoing fact is extremely important. Patients who marry after the age of 28 are contending, after a three

Journal of the American Medical Association


Studies of the human corpus luteum; corpus luteum-endometrial relationships in functional utering bleeding

American journal of obstetrics and gynecology


Cyclic changes in the physical and chemical properties of cervical mucus

Abstract: Cervical mucus at midcycle is increased in amount, acellularity, water content, and fluidity. Furthermore, cervical mucus at this time is well supplied with carbohydrate and presumably amino acids. From a teleologic standpoint, we may conclude that because of these characteristics the sperm, on deposition in the vagina, find an environment propitious for their nutrition and migration through the cervical canal.


Estrogen-Progesterone Therapy: A New Approach in the Treatment of Habitual Abortion


Thermogenic effect of progesterone

Thermogenic effect of progesterone


The Influence of Menstruation on Carbohydrate Tolerance in Diabetes Mellitus


Œstrogenic Activity of Alkylated Stilœstrols


Biopsy studies of human endometrium: criteria of dating and information about amenorrhea, menorrhagia, and time of ovulation

Abstract: Of 900 biopsies made with a small suction curet 457 from 329 women were analyzed to show the progression of the endometrium from the high-estrogen early-proliferative phase, immediately following menstruation, through the late proliferation occurring about Day 12 foll owing menstruation. Classifications from Days 14 to 27 are much easier to make because the 1st sign of progestin effect causes significant change. On Day 15 vacuolization of the cytoplasm and beginning migration of the nuclei toward the surface of the cells is seen, leaving a lucid zone underlying the nuclei. On Day 17 this zone is well-marked and the nuclei above it are lining up to lie later each beside the other near the middle of the cell. On Day 19 the row of nuclei has sunk distally near to the base of all the cells. On Day 18 a beginning edema of the stroma is seen, first in patches; by Day 21 it is generalized and the last vestige of the zona pellucida has disappeared. On Day 21 the process of secretion, which began about Day 17, is well advanced. From Day 21 on the signs of hormonal action are seen not primarily in the gla nds but in the stroma and vascular system. Edema has become generalized by Day 21; on Day 23 the stroma cells are larger, more thick-walled, and more numerous; by Day 25 the edema is replaced by masses of contiguous large cells with large pale nuclei and much cytoplasm; and on Day 26 size of the stroma cells has extended so that almost all the interglandu lar cells are contiguous. On Day 27 this solidification of the most sup erficial stroma becomes complete, the glands are widely dilated, the epithelium approaches the cuboidal, the vascular system is highly developed, and the arterioles and venules are engorged with blood. Late on Day 27, just before menstruation, lymphocytes and polymorphonuclear leukocytes appear in great numbers and erythrocytes appear in clumps. T he whole predeciduum is infiltrated, the stroma nuclei become pale, neutrophils appear in large numbers, the tissue disintegrates, and menstruation occurs. Understanding of this normal process can aid in clinical diagnosis of menstrual disorders. A series of biopsies taken with a small surgical curet does little tissue damage and can reveal hormonal imbalance, thin stroma associated with menopause or hypoplastic endometrium, and such pathological conditions as tuberculous endometritis and cancer of the endometrium. In the 3 cases in which a woman with unsuspected early pregnancy was biopsied, no harm was done. This study showed amenorrhea is usually due to deficient follicular development but may be present even if a proliferative endometrium shows a high degree of follicle activity; in the absence of pregnancy there is never a persistent corpus aluteum.


Amenorrhea Associated with Bilateral Polycystic Ovaries

Abstract: Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal


THE HORMONAL CAUSES OF PREMENSTRUAL TENSION

Abstract: My attention has been increasingly directed to a large group of women who are handicapped by premenstrual disturbances of manifold nature. It is well known that normal women suffer varying degrees of discomfort preceding the onset of menstruation. Employers of labor take cognizance of this fact and make provision for the temporary care of their employees. These minor disturbances include increased fatigability, irritability, lack of concentration and attacks of pain. In another group of patients, the symptoms complained of are of sufficient gravity to require rest in bed for one or two days. In this group, particularly, pain plays the predominant rôle. There is still another class of patients in whom grave systemic disorders manifest themselves predominantly during the premenstrual period. REPORT OF CASESCase 1. —A young, unmarried woman suffered from frequent convulsive attacks, which later occurred exclusively within ten days preceding menstruation. Neurologic investigation resulted in a diagnosis


Ovulationstermin und Konzeptionsfähigkeit bei der Frau


Eine neue Methode zur Bestimmung des Ovulationszeitpunkts


Metastatic or Embolic Endometriosis, due to the Menstrual Dissemination of Endometrial Tissue into the Venous Circulation


Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity

American Journal of Obstetrics and Gynecology


Illustrations of the Value of the Microscope in the Treatment of the Sterile  Condition


The Pathology and Treatment of Leucorrhœa


Creighton Model System & NaProTechnology: From Avoiding to Achieving Pregnancy

Abstract: *We are offering you a comprehensive look into women's health. By understanding natural methods and the science behind the menstrual period, the fundamental elements of conception and infertility can be easily understood.*


FACTS Elective Case: A Life Saving Fertility Surgery


About SREI

About SREI

Society for Reproductive Endocrinology and Infertility


Luteinized Unruptured Follicle Syndrome (LUFS) -- Ovulation's Master of Disguise

Abstract:
1. Attendees will be able to review the key clinical criteria for diagnosing LUF
2. Attendees will be able to list steps for medical management of LUF


Subspecialty certification: reproductive endocrinology and infertility

American Board of Obstetrics and Gynecology


Infertility surgery for men

Infertility surgery for men

Human Fertilisation & Embryology Authority

Abstract: Some men who don’t produce sperm naturally, or who have a blockage preventing sperm from coming out, can have surgery to increase their chances of conceiving. This includes men with fertility issues following chemotherapy and men who want to try and reverse a vasectomy. Surgical sperm extraction and vasectomy reversal are two common procedures.


AAPLOG Endometriosis & Surgery 101

AAPLOG Endometriosis & Surgery 101

Abstract: To discuss candidates for surgery, tools & techniques for endometriosis surgical treatment, as well as adhesion prevention measures


National ART Surveillance System (NASS)

National ART Surveillance System (NASS)

Centers for Disease Control and Prevention


RRM: Restorative Reproductive Medicine -- Restoring Health & Fertility without IVF

Abstract:
Creighton Model charting & scientific/physiological foundations
Creighton model data, and how it relates to the NaProTechnology application
Treatment approaches of NaProTechnology & Restorative Reproductive Medicine in gynecology and infertility
Benefits of RRM vs standard REI
Conditions and Treatments


Surgery for Male Infertility

Surgery for Male Infertility

Abstract: Urologists at NYU Langone sometimes recommend surgery to manage conditions that cause problems with sperm production in men with infertility. Surgical options include varicocelectomy, varicocele embolization, transurethral ejaculatory duct resection, vasectomy reversal, and microsurgical testicular sperm extraction.


Male Reproductive Surgery

Male Reproductive Surgery

Abstract: Overview of male reproductive surgery from UCSF's Center for Reproductive Health. Anatomical (surgical) male-factor problems can often be corrected with surgery, while some require medical therapy or assisted reproduction; effects on semen appear ~3 months after treatment (one spermatogenesis cycle). Covers varicocele (found in 42% of infertile men; semen improvement in ~67% and ~40% pregnancy after repair), vasectomy reversal (vasovasostomy with 85-99% return of sperm and 60-65% pregnancy with a healthy partner), ejaculatory duct obstruction (resection improves semen in ~70%, 20-30% pregnancy), and sperm-retrieval techniques (MESA, PESA, testicular extraction, testis mapping) used with IVF-ICSI when reconstruction is not possible.


Surgical Treatment for Male Infertility

Surgical Treatment for Male Infertility

Abstract: Surgical treatment for male infertility may include varicocelectomy, microsurgical reconstruction, vasectomy reversal, and epididymovasostomy. These procedures can help improve sperm movement, concentration, and structure, and can be effective in reversing blockages caused by vasectomy or other conditions. It is essential to find an experienced microsurgeon to perform these procedures. The Society for the Study of Male Reproduction provides resources and information for patients and physicians, including a directory of male infertility specialists and a patient education forum.

Society for the Study of Male Reproduction, Inc.