Mammary Stimulation Research Articles

How labor induction methods have evolved throughout history, from the Egyptian era to the present day: evolution, effectiveness, and safety

Induction of labor (IOL) is currently used for one in 10 pregnancies globally. Methods used for induction have shown major changes over time. Medical interventions trace their origins back to ancient civilizations, with evidence suggesting that they began over 5000 years ago in ancient Egypt. During this era, the Egyptians employed natural remedies such as castor oil and date fruits for the IOL. These early practices highlight the rich history and long-standing tradition of using natural substances in medical treatments, laying the foundation for the development of modern obstetric practices. After that, Hippocrates practiced mammary stimulation and mechanical cervical dilatation about 2500 years ago in Greece. Since then, there has been a marked change, especially over the last century, with the development of safer and more effective methods. Mechanical methods were the main method until the early 20th century, which were then substituted by pharmacological methods with more experiments in the mid to late 20th century. Nowadays, effectiveness, safety, cost, and client satisfaction are the main determinants of the methods used. This review summarizes how labor induction practices have evolved from the Egyptian era to the present-day randomized controlled trials and meta-analysis evidence, paying attention to their effectiveness, safety, and future directions.

Механизмы стимуляции роста аденокарциномы молочной железы мыши мезенхимными стволовыми клетками

Механизмы стимуляции роста аденокарциномы молочной железы мыши мезенхимными стволовыми клетками

Effect of stage of lactation and gestation on milking-induced hormone release in lactating dairy cows

Three experiments were conducted to better understand why milking-induced prolactin (PRL) release decreases as lactation advances. Experiment 1 compared the effects of milking, 2-min manual stimulation of the mammary gland (without milking), or injection of 1 IU of oxytocin (without milking) on hormonal release in early lactation cows, late-lactation and nongestating cows, and late-lactation and gestating cows (n = 6 per physiological status). Blood samples were collected from 20 min before the start of the treatments to 60 min after. During milking, PRL release (area under the curve above the baseline) was greater in the early lactation cows than in the late-lactation cows but was unaffected by gestation. Lactation stage and gestation did not affect PRL release by manual stimulation. Oxytocin did not induce a significant release of PRL or cortisol. Cortisol release was unaffected by physiological status and was similar for milking and mammary stimulation. Milking-induced β-endorphin release was not affected by physiological status. Experiment 2 compared the effects of milking, 2-min manual stimulation, or 10-min manual stimulation in cows in early (n = 6) and late (n = 6) lactation. Prolactin release was greater in the early lactation cows than in the late-lactation cows for all 3 treatments. A 10-min manual stimulation induced greater PRL release than a 2-min stimulation did. Cortisol release was greater in the early lactation cows but was similar among the 3 treatments. Experiment 3 compared the effects of a 5-min manual stimulation and the injection of domperidone (a dopamine antagonist) in cows in early (n = 6) and late (n = 6) lactation. Manually induced PRL release was greater in the early lactation cows than in the late-lactation cows. Prolactin release was greater with domperidone injection than with manual stimulation and was not affected by lactation stage. Thus, the reduction of milking-induced PRL release in late lactation is not a consequence of the lower sensitivity of the mammary gland to stimulation, a shorter milking time, the gestation stage, or the reduced capacity of the pituitary gland to secrete PRL.

Effect of mammary stimulation on dairy cows and heifers exposed to a lactation induction protocol

Cows (n = 21), dried off for a minimum of 45 days, and nulliparous heifers (n = 26), at ages > 18 months old, were placed on a 12-day Lactation Induction (LI) protocol. One group of animals (including both cows and heifers) received 3-minute mammary gland stimulation, along with the LI protocol. Another group, again including both cows and heifers, received no stimulation only the LI protocol This consisted of two injections of prostaglandin F2α (PGF2α; 25 mg) 11 days apart, followed by subcutaneous injections of 17β-estradiol (0.1 mg/kg BW/d) and progesterone (0.25 mg/kg BW/d) beginning 1 day later and continuing for seven (7) days. After this step, all animals received another injection of PGF2α on day 8, followed by intramuscular injections of reserpine (5 mg/d) and dexamethasone (20 mg/d) on each of days 9 to 12. All animals were milked, beginning on day 13, for a period of 154 days. For all animals, the success rate for lactation induction was 78% ± 6.3% and the mean weekly milk yield was 78.2 kg. Neither value was affected by mammary stimulation. Parity did not significantly impact on the success rate but it did affect the mean weekly milk yield. Milk yield varied significantly (p α = 0.05 level) affected by stimulation or by parity. However, heifers (at 8.2 weeks ± 1.0 week) tended (p = 0.1) to reach peak milk production earlier than cows (at 10.7 weeks ± 1.3). The milk produced was sold at a net profit per animal treated of $2206.31 TT. Hence, one can conclude that a Lactation Induction protocol can be a useful management tool to increase production and profitability of dairy operations in the tropics.

Efecto diferencial sobre el IGF-1 sérico de tibolona (5 mg/día) vs combinado continuo de estrógeno/progestina en mujeres postmenopáusicas

Tibolone has estrogenic, androgenic and progestational effects and is used in post menopausal women. It apparently has weaker effects on endometrial proliferation and mammary stimulation than conventional hormone replacement therapy. To compare the metabolic effects of tibolone (5 mg/day) and continuous combined conjugated estrogens/medroxyprogesterone acetate in postmenopausal women. Postmenopausal women, aged 45 to 60 years old, receiving estradiol valerate and medroxyprogesterone were included in the study. After a two months wash out period, in a double blind fashion, they were randomly assigned to oral tibolone 5 mg/day or equine conjugated estrogens 0.625 mg + medroxiprogesterone acetate 2.5 mg/day (ECE/MPA). At baseline, 30 and 45 days of treatment, fasting serum osteocalcin, somatomedin C (IGF-1, insulin-like growth factor 1), growth hormone (GH), and follicle stimulating hormone and first morning urine calcium and creatinine were measured. Thirty women were studied. There was more than 50% fall in urine calcium with either tibolone or ECE/MPA, while fasting GH or osteocalcin did not show significant changes. Serum IGF-1 increased significantly with tibolone at basal, 30 (+109%) and 45 days of treatment and did not change in the ECE/MPA group. Tibolone (5 mg/day) and ECE/MPA induced a similar reduction in urinary calcium. Tibolone increased serum IGF-1 levels. This may be due to undetected increment of overall GH secretion or to a specific action or IGF-1 generation from the liver and appears to be a novel differential effect of tibolone.

Fetal heart rate characteristics at 25 to 28 weeks' gestation.

The objective of this article is to define normative fetal heart rate (FHR) tracing characteristics between 25-28 weeks' gestation in a low-risk population with normal pregnancy outcomes and to determine which criteria best determine FHR reactivity. Continuous FHR tracings were reviewed from 188 low-risk women participating in a trial of the Mammary Stimulation Test (MST) at 25-28 weeks' gestation. A reactive tracing required the presence of > or =two accelerations in 20 min. Different acceleration criteria were evaluated based upon the width of the acceleration (short vs. long) and the amplitude of the acceleration (10 vs. 15 bpm). Seventy-one percent of the FHR tracings were reactive using the higher amplitude (15 bpm), short criteria. This number increased significantly to 92% when the lower amplitude (10 bpm), short criteria were used (p <0.01). As gestational age advanced, there was a trend toward increased reactivity irrespective of which criteria were used, but these differences were not significant. Reducing the acceleration amplitude criteria to 10 bpm in preterm pregnancies will maximize the number of reactive nonstress tests. This is advantageous because it would improve test specificity and decrease the false-positive rate. Our findings need to be prospectively validated in a high-risk population.

Prediction of preterm birth in nulliparous patients

Our goal was to determine whether the mammary stimulation test combined with a risk scoring system and cervical examination at 26 to 28 weeks' gestation could effectively identify private nulliparous patients at risk for spontaneous preterm birth. The mammary stimulation test was performed by 267 nulliparous patients with singleton gestations at 26 to 28 weeks. Risk scores were determined by the method of Creasy et al. and cervical examinations were performed at the first prenatal visit and at 26 to 28 weeks. Summary predictive values were calculated for each test, and a stepwise discriminate analysis was performed. Spontaneous preterm birth occurred at < 37 weeks in 26 of 265 (9.8%) patients. The following variables were independently associated with spontaneous preterm birth: positive result of mammary stimulation test, risk score > or = 10, soft cervix at 26 to 28 weeks, bacteriuria, and current smoking. The best discriminate model included positive result of mammary stimulation test, soft cervix, bacteriuria, current smoking, and prior spontaneous abortion(s). This model identified 19 patients as being at risk for spontaneous preterm birth with sensitivity of 35%, specificity of 96%, and positive predictive value of 47%. Combining the mammary stimulation test with a cervical examination at 26 to 28 weeks' gestation and routinely obtained prenatal data correctly identified 35% of spontaneous preterm births in nulliparous patients with a positive predictive value of 47%. Prospective validation of this model is warranted.

Mammary stimulation test predicts preterm birth in nulliparous women

OBJECTIVE: This prospective clinical trial was designed to assess the ability of the mammary stimulation test to predict preterm birth in a private nulliparous population. STUDY DESIGN: The mammary stimulation test was performed between 26 and 28 weeks' gestation by 267 nulliparous women with singleton pregnancies. Test results were blinded to both patient and referring physician. Pregnancy outcome data were collected from the perinatal database and medical records. RESULTS: The mammary stimulation test was positive in 45 of 266 (17%) patients. Delivery occurred at <37 weeks in 27 patients (10.2%) and at <34 weeks in five (1.9%). The mammary stimulation test demonstrated a sensitivity of 37%, a specificity of 84%, a positive predictive value of 20%, and a negative predictive value of 92% for delivery at <37 weeks' gestation. For delivery at <34 weeks' gestation the mammary stimulation test had a sensitivity of 60%, a specificity of 82%, a positive predictive value of 6%, and a negative predictive value 99%. The odds ratio for delivery at <37 weeks was 3.0 (95% confidence interval 1.3, 7.1), and for delivery at <34 weeks the odds ratio was 7.0 (95% confidence interval 1.1, 43.0). One third of preterm deliveries were secondary to idiopathic preterm labor, and the mammary stimulation test was positive in 77.8% (seven of nine) of these pregnancies. Patients with a positive test were more likely to require observation in labor and delivery for preterm uterine contractions (34% vs 4.3%, p < 0.01), and they were more likely to demonstrate change at cervical examination (14% vs 2%, p < 0.01). CONCLUSION: In this population traditionally considered to be at low risk for preterm birth a positive mammary stimulation test was useful in identifying patients at risk for preterm uterine activity and preterm birth. Equally important was the identification of women who were at low risk for preterm birth. (AM J Obstet Gynecol 1994;170:1809-14.)

Mammary stimulation test predicts preterm birth in nulliparous women

Objective: This prospective clinical trial was designed to assess the ability of the mammary stimulation test to predict preterm birth in a private nulliparous population. Study Design: The mammary stimulation test was performed between 26 and 28 weeks' gestation by 267 nulliparous women with singleton pregnancies. Test results were blinded to both patient and referring physician. Pregnancy outcome data were collected from the perinatal database and medical records. Results: The mammary stimulation test was positive in 45 of 266 (17%) patients. Delivery occurred at < 37 weeks in 27 patients (10.2%) and at < 34 weeks in five (1.9%). The mammary stimulation test demonstrated a sensitivity of 37%, a specificity of 84%, a positive predictive value of 20%, and a negative predictive value of 92% for delivery at < 37 weeks' gestation. For delivery at < 34 weeks' gestation the mammary stimulation test had a sensitivity of 60%, a specificity of 82%, a positive predictive value of 6%, and a negative predictive value 99%. The odds ratio for delivery at < 37 weeks was 3.0 (95% confidence interval 1.3, 7.1), and for delivery at < 34 weeks the odds ratio was 7.0 (95% confidence interval 1.1, 43.0). One third of preterm deliveries were secondary to idiopathic preterm labor, and the mammary stimulation test was positive in 77.8% (seven of nine) of these pregnancies. Patients with a positive test were more likely to require observation in labor and delivery for preterm uterine contractions (34% vs 4.3%, p < 0.01), and they were more likely to demonstrate change at cervical examination (14% vs 2%, p < 0.01). Conclusion: In this population traditionally considered to be at low risk for preterm birth a positive mammary stimulation test was useful in identifying patients at risk for preterm uterine activity and preterm birth. Equally important was the identification of women who were at low risk for preterm birth. Objective: This prospective clinical trial was designed to assess the ability of the mammary stimulation test to predict preterm birth in a private nulliparous population. Study Design: The mammary stimulation test was performed between 26 and 28 weeks' gestation by 267 nulliparous women with singleton pregnancies. Test results were blinded to both patient and referring physician. Pregnancy outcome data were collected from the perinatal database and medical records. Results: The mammary stimulation test was positive in 45 of 266 (17%) patients. Delivery occurred at < 37 weeks in 27 patients (10.2%) and at < 34 weeks in five (1.9%). The mammary stimulation test demonstrated a sensitivity of 37%, a specificity of 84%, a positive predictive value of 20%, and a negative predictive value of 92% for delivery at < 37 weeks' gestation. For delivery at < 34 weeks' gestation the mammary stimulation test had a sensitivity of 60%, a specificity of 82%, a positive predictive value of 6%, and a negative predictive value 99%. The odds ratio for delivery at < 37 weeks was 3.0 (95% confidence interval 1.3, 7.1), and for delivery at < 34 weeks the odds ratio was 7.0 (95% confidence interval 1.1, 43.0). One third of preterm deliveries were secondary to idiopathic preterm labor, and the mammary stimulation test was positive in 77.8% (seven of nine) of these pregnancies. Patients with a positive test were more likely to require observation in labor and delivery for preterm uterine contractions (34% vs 4.3%, p < 0.01), and they were more likely to demonstrate change at cervical examination (14% vs 2%, p < 0.01). Conclusion: In this population traditionally considered to be at low risk for preterm birth a positive mammary stimulation test was useful in identifying patients at risk for preterm uterine activity and preterm birth. Equally important was the identification of women who were at low risk for preterm birth.

Predicting Prematurity: The Mammary Stimulation Test

The MST appears to have theoretical rationale, predictive utility, simplicity, safety, and low cost that suggests that its routine use in prematurity prevention may ultimately save significant health care dollars. Presently, the MST should be used as an adjunct to prenatal care until further and more definitive investigation has been conducted; however, it seems promising that the MST will provide some reassurance in patients with negative tests and signify patients that are at significant risk for premature delivery (positive MST). It is hoped that further investigation will validate the MST's use in prematurity prevention in order to help decrease the incidence of preterm delivery.

The mammary stimulation test—A predictor of preterm delivery?

Clinical risk identification for preterm delivery, the major cause of perinatal morbidity and mortality, remains problematic. To test the hypothesis that a provocative test for uterine contractility at the beginning of the third trimester would reliably identify patients destined to be delivered before and at term, we designed the mammary stimulation test. Uterine contractions in response to nipple stimulation at a mean of 28.6 weeks' gestation, were evaluated in 94 gravid patients at risk for preterm delivery. The mammary stimulation test, the results of which were not used for clinical management, was positive in 50% of patients tested and had a sensitivity of 84% and a positive predictive value of 34% (chi 2 = 11.15, p less than 0.01). Ninety-four percent of patients predicted to be delivered at term actually were delivered at term (negative predictive value). Furthermore, no patients with a negative mammary stimulation test were delivered within 1 month of testing or were delivered of infants weighing less than 2000 gm. Discriminant analysis indicated that the mammary stimulation test provided information beyond that available from clinical risk factors alone. A cost analysis suggested that the use of the mammary stimulation test could reduce the cost of ambulatory uterine activity monitoring by nearly 50%. If these findings can be validated in additional samples, the mammary stimulation test may be useful in prematurity prevention programs.

465 Early identification of risk for preterm labor and delivery: The information content of the morphometry of a positive mammary stimulation test (MST)

465 Early identification of risk for preterm labor and delivery: The information content of the morphometry of a positive mammary stimulation test (MST)

Mammary stimulation and maternal aggression in rodents: thelectomy fails to reduce pre- or postpartum aggression in rats

In mice, tactile stimulation of the nipples appears to be critical for the onset of postpartum maternal aggression. Surgical removal of the nipples (thelectomy) blocks aggression if performed prior to parturition. In rats, indirect evidence suggests a similar role for nipple stimulation in maternal aggression. Two experiments were undertaken to determine whether thelectomy prior to mating reduces pregnancy-induced and/or postpartum aggression in this species. In the first, thelectomized and sham-thelectomized females were subjected to homecage tests (pups, if any, present) with unfamiliar male intruders on Gestation Days 18 and 21 and Lactation Days 3 and 5. Additional groups of thelectomized females were tested one time only on either Lactation Day 5 or 12. Thelectomized and control females were equally aggressive; postpartum, nearly all females in both groups attacked. Experiment 2 used females that were hysterectomized-ovariectomized (HO) on Gestation Day 16. Such females are not aggressive prior to initiating maternal behavior, but become highly aggressive (over 80% attacking) after commencing maternal care. Females again were thelectomized or shamthelectomized prior to mating. On Day 16 HO was performed, and 48 hr later continuous exposure to pups was begun. After the females had displayed maternal behavior for 1.5–2 days, intruder tests were conducted. All females attacked at least once, with no differences between treatment groups. Thus thelectomy does not reduce maternal aggression in the rat. This finding, however, does not preclude a role for tactile ventral stimulation in mediating maternal aggression.

Neural and anatomic characteristics of peripheral afferent fibers in the milk ejection reflex

Conduction velocities were measured and certain morphologic characteristics were examined of the abdominal mammary nerve in two- to ten-day postpartum rats. This nerve enters the spinal cord at the spinal segmental level T-12. Overall conduction velocity was (Mean±S.D.) 18.9±2.25 m/sec with a major peak at 9.7±0.72 m/sec. The distribution of conduction velocities in the nerve was similar to that of a typical spinal nerve. Nerve fiber diameters measured between about 1 and 25 microns with peaks at 4.9, 10.5, and 18.9 microns. Injection into the peripheral nerve of fluorescent dye, Lucifer yellow CH (LY), or wheat germ agglutinin-coupled horseradish peroxidase (WGA-HRP) after ventral root rhizotomy permitted study of the distribution of primary afferents in the spinal cord. The terminal field of these fibers centered around the dorsal cap of Clarke's column and the lateral spinal nucleus, bilaterally. The distribution of WGA-HRP was more restricted than that of LY. A large number of LY-staining fibers were also found ipsilaterally in the medial portion of the intermediomedial column. A smaller amount of LY-staining was present contralaterally in the area of the spinothalamic tract. It is concluded that afferent impulses resulting from mammary stimulation in the milk ejection reflex are probably carried in a mixed spinal nerve whose primary afferent field lies mainly in ipsilateral spinal structures, although there is some evidence for crossing fibers. The data suggest that considerable opportunity exists for interaction with major sensory afferent fiber systems as well as with autonomic fibers. Hence, the spinal path of afferent information relevant for the milk ejection reflex may well be diffuse and it may involve several sensory modalities.

Reflex Regulation of Autonomic Influences upon the Oxytocin-Induced Contractile Response of the Mammary Gland in the Anesthetized Rat*

Intramammary pressure (IMP) from an abdominal mammary gland, generated in response to intrajugular injections of oxytocin, were recorded before, during, and after 120–140 sec of electrical stimulation of the cut central end of a contralateral mammary nerve in the urethane-anesthetized lactating rat. The stimulation parameters were 5- to 30-V 1-msec pulses at a frequency of 10/sec. The amplitude of the IMP responses to a given dose of oxytocin was reduced by about 50% when tested after 60 and 120 sec of electrical stimulation and recovered to prestimulus heights 3–10 min after cessation of the stimulus. The depressant effect of nerve stimulation then could be repeated. Bilateral adrenal ligature, iv injection of 0.3 mg propranolol, or section of the spinal cord above the level of entry of the mammary nerve completely blocked the depressant effect of nerve stimulation. In fact, the slope and amplitude of the IMP response eventually increased above that found before mammary nerve stimulation after each of th...

Correlation between the effects of neuroleptics on prolactin release, mammary stimulation and the vaginal cycle in rats.

The correlation between hyperprolactinaemia induced by the administration of neuroleptic drugs, disturbances of the vaginal cycle and mammary gland stimulation in rats was investigated as a test model simulating the clinical syndrome of hyperprolactinaemia and amenorrhoea with anovulation. In acute experiments in which clozapine, sulpiride and chlorpromazine were administered orally to rats of both sexes, there were rapid increases in the level of prolactin in the serum with peak values between 15 and 60 min. The responses of female rats to various doses of sulpiride were consistently higher than those of male rats. Hyperprolactinaemia induced by sulpiride in dioestrous rats failed to desensitize the ovaries to the ovulatory effect of exogenous luteinizing hormone releasing hormone. Studies of these substances and of metoclopramide, haloperidol and thioridazine were then carried out in females rats by daily oral administration over a period of 13 days. The increases in the level of prolactin in the serum were paralleled by disruption of the vaginal cycle up to and including constant dioestrus and by mammary gland stimulation which, like the preceding phenomena, showed dose-dependence. The potencies of these six neuroleptics, as estimated from their effects on the mammary gland, appeared to be haloperidol greater than sulpiride greater than or equal to metoclopramide = thioridazine greater than chlorpromazine greater than clozapine.

Triamcinolone-induced mammary activation in virgin mice

Intact ICR mice receiving Triamcinolone showed extensive proliferation within the mammary gland. Galactophores and ducts were enlarged. In contrast with the non-treated animals, those treated with Triamcinolone had an evident lobuloalveolar system. Triamcinolone failed to activate the glands of oophorectomized animals. It is thus evident that systemic administration of Triamcinolone to yound virgin mice causes mammary stimulation and that this effect only occurs in the presence of the ovary.

Problems in evaluating chronic toxicity of contraceptive steroids in dogs.

The long-term effects of oral contraceptive steroids including a combination of norethindrone and ethynylestradiol, a sequential regimen of dimethisterone and ethynylestradiol, and daily administration of megestrol acetate were studied in female beagle dogs at dose levels of 1, 10, or 25 times the projected human dose levels. The major findings included cystic endometrial hyperplasia and pyometra requiring hysterectomies and alopecia for the norethindrone-ethynylestradiol and dimethisterone-ethynylestradiol treated dogs. These groups did not have accentuated mammary development or treatment-related hyperplastic or neoplastic changes. For dogs given dimethisterone-ethynylestradiol, numerous acne-like lesions occurred in the skin of the mammary areas. Dogs given the higher dose levels of megestrol acetate had marked mammary stimulation, hyperplastic and neoplastic changes in the mammary glands, and clinical and pathologic changes typical of diabetes mellitus. Mammary changes of nodular hyperplasia, benign mixed tumor, and adenocarcinoma appeared as distinct entities although constant and intense mammary stimulation may be a common denominator. Such mammary changes have not been found in long-term studies in monkeys or rats with megestrol acetate, and the relevance of the canine mammary changes to projecting potential tumorigenesis in women is questioned.

Mammary stimulation causes prolactin secretion in non-lactating women.

VARIOUS afferent neurogenic stimuli to the chest wall or breast have been associated with galactorrhoea in man. Non-puerperal lactation has been reported following mechanical trauma, surgery, or burns of the chest wall or breast1–4; following herpes zoster of the chest wall3; and induced by poorly fitting garments4 or breast manipulation3,4. Lactation has occurred in men in association with prolonged suckling of the breast1,3 and may occur in nulliparous and post-menopausal women in response to a suckling stimulus5,6.

Influence of Prior Pseudopregnancy on Lactation and Reproduction of Rats

Conflicting opinions exist regarding the effect of parity (lactation number) on mammary development and milk yield. The cumulative effect of successive pregnancies is difficult to distinguish from other effects accompanying advancing age, increases in body size, or digestive capacity.Pseudopregnancy in the rat, produced by mating with vasectomized males, causes an 11–12 day stimulation of the mammary gland similar to that of early pregnancy. To study the effect of prior mamary stimulation, rats were compared that had a) two prior pseudopregnancies, b) one prior pseudopregnancy, and c) no such previous mammary stimulation. These rats, of equal age, were subsequently bred to intact males and their reproductive and milk-producing performance determined.Rats stimulated by two pseudopregnancies showed a 15% increase in litter size, but this difference in reproductive preformance was not statistically significant. All litters were standardized at birth to ten young and weighed periodically to determine the lactational performance of the dam. Growth of the litters, number of young surviving, and dam weight at weaning were similar for all groups. This experiment thus indicates that the prior mammary stimulation afforded by pseudopregnancy did not increase milk production in the subsequent natural lactation.