OG Updates

·         The reduced gastrointestinal motility during pregnancy has been thought to be due to increased circulating levels of progesterone. However, recent evidence suggests that elevated estrogen concentrations mediate the effect by enhancing nitric oxide release from the nonadrenergic noncholinergic nerves that modulate gastrointestinal motility. Gastric emptying has generally been considered to be slowed during pregnancy; however, via indirect methods some researchers have shown no changes in gastric emptying rates in women in the first or second trimesters or at term. Transit time of food through the gastrointestinal tract may be slowed so much that more water than normal is reabsorbed, leading to constipation.

·         Prothrombin (factor II) is only slightly affected by pregnancy, if at all. Some investigators have noted small increases; others have reported normal values. Recent studies have also noted mild increases in factor V, and suggest a thrombinlike influence on the activity of factor V. Factor XI decreases slightly toward the end of pregnancy, and factor XIII (fibrin-stabilizing factor) is appreciably reduced, up to 50% at term.

·         The physiologic hypertrophy of the pituitary gland is associated with an increase in the number of pituitary lactotroph cells at the expense of the somatotropic cell types. Thus, growth hormone secretion is depressed during the second half of pregnancy and the early puerperium. Because levels of circulating insulin-like growth factor (IGF-1) increase throughout pregnancy, a placental growth hormone has been postulated and recently identified. Maternal levels of IGF-1 correlate highly with this distinct placental growth hormone variant but not placental lactogen during pregnancy and in the immediate puerperium.

·         Ultrasound has had a continuous evolution over the last 20 years, with better equipment being produced each year. Real-time sonography allows a 2-D image to demonstrate fetal anatomy, as well as characteristics such as fetal weight, movement, volume of amniotic fluid, and structural anomalies such as myomas or placenta previa which may affect the pregnancy. 3-D sonography allows volume to be ascertained, creating a three-dimensional appearing image on the 2-D screen, which assists in identifying certain anatomical anomalies. Most recently, 4-D machines have been developed, which produce a 3-D image in real time.

·         Recent studies of the uterine artery early diastolic notch have demonstrated its usefulness as another marker for fetal well-being.

·         Maternal diabetes, whether it is gestational, chemical, or insulin-dependent, is the condition classically associated with fetal macrosomia. It was long assumed that fetal macrosomia could be accounted for by the “Pedersen hypothesis”—ie, that the condition was due to inadequate management of diabetes during pregnancy. Initial reports suggested that careful control of blood glucose in insulin-dependent diabetic women would prevent fetal macrosomia, but recent studies have suggested that the problem is not so simple and that the incidence may correlate better with cord blood concentrations of maternally acquired anti-insulin IgG antibodies, and/or increased serum levels of free fatty acids, triglycerides, and the amino acids alanine, serine, and isoleucine.

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·         Preeclampsia is hypertension associated with proteinuria and edema, occurring primarily in nulliparas after the 20th gestational week and most frequently near term. Recent data support the elimination of edema as a diagnostic criterion. Eclampsia is the occurrence of seizures that cannot be attributed to other causes in a preeclamptic patient.

·         While early studies failed to show a significant increase in cerebrospinal fluid (CSF) magnesium concentrations during therapy, more recent studies have shown about a 20% increase in CSF magnesium levels, and these levels parallel those in the serum. Magnesium sulfate decreases the amount of acetylcholine released at the neuromuscular junction, resulting in peripheral neuromuscular blockade at high magnesium concentrations; however, this does not account for its anticonvulsant effect. A recent study demonstrated that magnesium sulfate had a central anticonvulsant effect on electrically-stimulated hippocampal seizures in rats. The researchers speculated that since magnesium ion blocks calcium entry into neurons through the N-methyl-D-aspartate (NMDA) receptor–operated calcium channel, magnesium sulfate might be acting through this mechanism. On the other hand, another study found that magnesium sulfate was ineffective in altering seizure discharge in pentylenetetrazole-induced status epilepticus in rats. These researchers argued that because magnesium blocks calcium entry through the NMDA receptor–operated calcium channel in a voltage-dependent manner, it would be ineffective in neurons that are continuously depolarizing as in status epilepticus. Finally, Doppler studies of brain blood flow in preeclamptic women suggest that magnesium sulfate vasodilates the smaller-diameter intracranial vessels distal to the middle cerebral artery and may exert its main effect in the prophylaxis and treatment of eclampsia by reversing vasospastic cerebral ischemia.

·         D-Dimer or fibrin split products are useful when abruptio placentae is suspected. These are the most sensitive tests to confirm coagulopathy; however, they are qualitative studies and give little information about the severity of abruption. Recent literature has demonstrated a correlation between elevated CA-125 levels and abruption. This assay has little clinical utility, as it usually requires a long turnaround time. A Kleihauer-Betke test may be useful in the Rh-negative patient. The results are useful in calculating the appropriate dose of Rh immune globulin.

·         The use of erythropoietin was found to increase production of hemoglobin F in baboons; however, it stimulated hemoglobin S production in humans. Hemoglobin F synthesis by stimulating Y-chain production appears to be a promising form of therapy for the sickle cell disease and thalassemia syndrome. Y-chains of hemoglobin F inhibit polymerization of hemoglobin S and therefore inhibit sickling. Recombinant erythropoietin and hydroxyurea have been used together recently with elevation of hemoglobin F. More recently intravenous arginine butyrate has been used with the increase in fetal globin synthesis, production of F reticulocytes, and the level of Y-globin.

·         In recent years the diagnosis of persistent hyperemesis gravidarum has been linked to Helicobacter pylori infection.

·         Previously, it was thought that a hormonal imbalance was related to the clinical manifestations of PMS/PMDD, but the most recent consensus is that physiologic ovarian function is the trigger. This is supported by the efficacy of ovarian cyclicity suppression, either medically or surgically, in eliminating premenstrual complaints.

Further research has shown that serotonin (5-HT), a neurotransmitter, is important in the pathogenesis of PMS/PMDD. Both estrogen and progesterone have been shown to influence the activity of serotonin centrally. Many of the symptoms of other mood disorders resembling the features of PMS/PMDD have been associated with serotonergic dysfunction.

·         Recent evidence indicates that spermicides containing nonoxynol-9 (N-9) are not effective in preventing cervical gonorrhea, chlamydia or HIV infection. In addition, frequent use of spermicides containing N-9 has been associated with genital lesions which may be associated with an increased risk of HIV transmission.

·         Three additional hormonal contraceptives methods have recently become available: The transdermal patch (Ortho Evra, Ortho-McNeil Pharmaceuticals, Inc.), the vaginal ring, (NuvaRing, Organon, Inc.) and a single rod implant system (Implanon, Organon, Inc.).

·         Recently, surgically implantable device like Interstim have been found very useful in patients with intractable urgency incontinence and voiding dysfunction.

·         Many surgeons encourage their patients to sip tap water (not ice water) on the first day after uncomplicated gynecologic surgery. On the following day, clear fluids are often given if bowel sounds are normal, and solid food usually is withheld until the patient passes flatus. Some recent studies suggest that early oral intake (clear liquids on postoperative day 1), even among patients with major abdominal surgery, reduces length of hospitalization and is not associated with an increased incidence of ileus.

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·         Recently, new factors have been discovered that are involved with the regulation of bone remodeling: osteoprotegerin, a naturally-occurring protein with potent osteoclastogenesis inhibitory activity; and RANKL (receptor activator of nuclear factor kappa beta ligand), a transmembrane ligand expressed on osteoblasts.

Gynecology Facts from Previous Papers

·         The literature does not support an increased risk of squamous cell carcinoma of the cervix in women who smoke.

·         For postcoital testing, sexual intercourse should be done on which day of menstrual cycle – Day 14

·         OCPs – Oral contraceptive pills give protection against the following conditions :

THE COBRAS UFO POEM

1. T = Thyroid autoimmune disorders

2. H = Hirsutism

3. E = Endometrial carcinoma

4. C = Colorectal cancer

5. O = Ovarian cancer

6. B = Benign Breast diseases ( fibroadenosis )

7. R = Rheumatoid arthritis

8. A = Anemia and Acne

9. S = Salpingitis ( PID )

10. U = Uterine cancer

11. F = Fibroids ( exception is submucous variety )

12. O = Ovarian cysts

13. P = Pelvic inflammatory disease

14. O = Osteoporosis and Osteopenia

15. E = Ectopic pregnancy

16. M = Mittelschmerz , Menorrhagia , Dysmenorrhea , Premenstrual Tension , Polymenorrhea .

Other important points to be remembered about OCPs is that their extensive use leads to a few diseases like :

1. Cancer cervix

2. Breast cancer

3. Pituitary adenoma

4. Hepatic adenoma

·         absolute contraindications of oral contraceptive pills:

ü  carcinoma of breast and genitals

ü  congenital hyperlipidemia

ü  porphyria

ü  cardiac abnormalities

ü  moderate to severe hypertension

ü  previous or present history of thromboembolism

ü  undiagnosed abnormal uterine bleeding

ü  impending major surgery to avoid post operative thromboembolism

ü  liver diseases , hepatoma or history of jaundice during past pregnancy 

·         conditions in which GnRH analogues are used :

ü  adenomyosis

ü  irritable bowel syndrome

ü  carcinoma breast

ü  DUB

ü  endometriosis

ü  fibromyoma uterus

ü  hirsutism

ü  infertility

ü  precocious puberty

Miscellaneous Gynecology

·         After obtaining the history and physical examination and evaluating a urinalysis (including urine culture), initial evaluation of the incontinent patient includes a cystometrogram, check for residual urine volume, stress test, and urinary diary.

The primary reason to perform a cystometrogram is to rule out uninhibited detrusor contractions.

·         Partial colpocleisis by the Le Fort procedure is reasonable for elderly patients who are not good candidates for vaginal hysterectomy and A&P (anterior and posterior) repair as treatment for vaginal and uterine prolapse. Urinary incontinence can be a side effect of this procedure, so care must be exercised in the denudation of vaginal mucosa near the bladder. In a patient who already has urinary incontinence, the Le Fort operation would be relatively contraindicated.

·         The degree or severity of pelvic relaxation is rated on a scale of 1 to 3, based on the descent of the organ or structure involved. First-degree prolapse involves descent limited to the upper two-thirds of the vagina. Second-degree prolapse is present when the structure is at the vaginal introitus. In cases of third-degree prolapse, the structure is outside the vagina. Total procidentia of the uterus is the same as a third-degree prolapse, which means that the uterus would be located outside the body.

Menopause

·         Women over 65 should have all of the following immunizations: tetanus-diphtheria booster every 10 years, influenza virus vaccine annually, and a one-time pneumococcal vaccine. A hepatitis B vaccine would be indicated only in individuals at high risk, i.e., international travelers, intravenous drug users and their sexual contacts, those who have occupational exposure to blood or blood products, persons with chronic liver or renal disease, or residents of institutions for the developmentally disabled and of correctional institutions.

·         Women over 65 years old should undergo cholesterol testing every 3 to 5 years, fasting glucose testing every 3 years, screening for thyroid disease with a TSH every 3 to 5 years, and periodic urinalysis. CA-125 testing is not recommended for ovarian cancer screening in women who are at low risk for ovarian cancer. A urinalysis that is positive for blood should be followed up with a urine culture to detect an asymptomatic urinary tract infection before further workup is done or referral to a urologist is made.

·         The two most common causes of urinary incontinence are stress (loss of urine due to increased intra-abdominal pressure [e.g., with cough or sneeze]) and detrusor instability (urgency accompanies incontinence).

1.Stress incontinence may include topical estrogens, medications to increase sphincter tone, pelvic muscle rehabilitation, and surgical approaches.

One of the abdominal procedures that successfully cures stress incontinence is the Marshall-Marchetti-Krantz (MMK) procedure, which involves the attachment of the periurethral tissue to the symphysis pubis. However, in approximately 3% of patients undergoing the procedure, the painfully debilitating condition of osteitis pubis will develop. Treatment of this aseptic inflammation of the symphysis is suboptimal, and the course is usually chronic. An alternative procedure (the Burch procedure) was therefore introduced; this involves the attachment of the periurethral tissue to Cooper’s ligament. The incidences of urinary retention, recurrent urinary tract infections, and failure are essentially the same in the MMK and Burch procedures. Other procedures commonly employed in the treatment of stress incontinence are anterior repair and needle urethropexy (Stamey-Pererya procedure – Sling procedure). The traditional anterior repair, or Kelly plication, has a 5-year failure rate of approximately 50%. The initial cure rate (90%) for the Stamey-Pererya procedure appears to equal that for the Burch or MMK procedures. Kegel exercises may strengthen the pelvic musculature and improve bladder control in women with stress urinary incontinence.

The success rate of the suburethral sling procedure to treat intrinsic urethral sphincter dysfunction is 80-90%. Periurethral bulking injections with GAX-collagen have a lower success rate of 45-65%

2. Detrusor instability is treated with behavioral modification and medications to control involuntary contractions.

Urge incontinence is the involuntary loss of urine associated with a strong desire to void. Most urge incontinence is caused by detrusor or bladder dyssynergia in which there is an involuntary contraction of the bladder during distension with urine. The management of urge incontinence includes bladder training, biofeedback, or medical therapy. Treatment with anticholinergic drugs (oxybutynin chloride), β-sympathomimetic agonists (metaproterenol sulfate), Valium, antidepressants (imipramine hydrochloride), and dopamine agonists (Parlodel) has been successful. These pharmacologic agents will relax the detrusor muscle. In postmenopausal women who are not on estrogen replacement therapy, estrogen therapy may improve urinary control.

Multichannel urodynamic study should be done for patients with stress incontinence prior to surgical correction and in patients with urge incontinence not responsive to medical therapy.

·         Dyspareunia, which is genital pain associated with intercourse, and vaginismus, which involves involuntary spasm of the muscles of the outer third of the vagina, preventing vaginal penetration.

·         Hormone replacement therapy is recommended for treatment of vasomotor symptom and urogenital atrophy and to decrease the risk of vertebral and hip fractures.

·         Lichen sclerosus was formerly termed lichen sclerosus et atrophicus, but recent studies have concluded that atrophy does not exist. Patients with lichen sclerosus of the vulva tend to be older; they typically present with pruritus, and the lesions are usually white with crinkled skin and well-defined borders. The histologic appearance of lichen sclerosus includes loss of the rete pegs within the dermis, chronic inflammatory infiltrate below the dermis, the development of a homogenous subepithelial layer in the dermis, a decrease in the number of cellular layers, and a decrease in the number of melanocytes. Mechanical trauma produces bullous areas of lymphedema and lacunae, which are then filled with erythrocytes. Ulcerations and ecchymoses may be seen in these traumatized areas as well. Mitotic figures are rare in lichen sclerosus, and hyperkeratosis is not a feature. While a significant cause of symptoms, lichen sclerosus is not a premalignant lesion. Its importance lies in the fact that it must be distinguished from vulvar squamous cancer.

·         Current studies to watch for menopause:

1. Kronos Early Estrogen Prevention Study (KEEPS) is an ongoing study evaluating estrogen given either orally or transdermally to recently postmenopausal women to see if starting HT earlier modifies the effect on atherosclerotic disease. Progesterone is given to women who have their uterus.
2. The Early versus Late Intervention Trial with Estradiol (ELITE) study is currently evaluating women less than 6 years postmenopausal versus women greater than 10 years postmenopausal and the effect of estradiol on the development of atherosclerotic changes. Progesterone is given to women with their uterus.
3. The Study of Women Across the Nation (SWAN) is observing midlife transition and normal aging in women of five different American ethnic groups.

Gynecology Oncology

·         Fibroadenomas are the second most common benign breast disorder, after fibrocystic changes. They are characterized by being firm, solid, nontender, and freely mobile. Fibroadenomas have an average size diameter of 2.5 cm and are well circumscribed. These lesions most commonly occur in adolescents and women in their twenties. Fibrocystic changes occur in about one-third to one-half of reproductive-age women and represent an exaggerated response of the breast tissue to hormones. Patients with fibrocystic changes complain of bilateral mastalgia and breast engorgement preceding menses. On physical exam, diffuse bilateral nodularity is typically encountered. Cystosarcoma phyllodes are rare fibroepithelial tumors that constitute 1% of breast malignancies. These rapidly growing tumors are the most frequent breast sarcoma and occur most frequently in women in the fifth decade of life. Trauma to the breast can result in fat necrosis. Women with fat necrosis commonly present to the physician with a firm, tender mass that is surrounded by ecchymosis. Occasional skin retraction can occur, making this lesion difficult to differentiate from cancer. It is unlikely that this patient who presents in her twenties has breast cancer.

·         The Gail model is a computer model that analyzes a woman's various risk factors to give her an "accurate," individualized risk assessment. This model includes some of the above identified risk factors. It does not include whether or not a woman has been tested for the BRCA gene. It also does not consider the use of HRT.

·         The vagina as a secondary site of another cancer is more common than primary vaginal cancer.

·         Extensive evidence indicates that infection with certain high-risk subtypes of human papilloma virus (HPV) (types 16, 18, 31, 45, 51-53, 58, or 58) is an important etiologic event. Though the exact mechanism of malignant transformation has not been entirely elucidated, it is clear that HPV oncoproteins E6 and E7 impair proliferation inhibition by blocking the function of the p53 and retinoblastoma tumor suppressor pathways.

·         There is no screening method for ovarian cancer since CA-125 is nonspecific and transvaginal ultrasound is not cost-effective.

·         The term Krukenberg tumor describes metastatic adenocarcinoma of the ovary that contains significant numbers of signet ring cells in a cellular ovarian stroma.

·         When you teach a patient to perform a breast self-exam, you should recommend that it be performed monthly, a few days after the menses. It is best to perform the breast exam in both the erect and supine positions. Asymmetry of the breasts is common in most women, but any recent changes need to be reported. Any nipple discharge should be reported immediately to a physician, because it can be associated with an underlying tumor.

·         The main routes of spread of cervical cancer include vaginal mucosa, myometrium, paracervical lymphatics, and direct extension into the parametrium. The prevalence of lymph node disease correlates with the stage of malignancy. Primary node groups involved in the spread of cervical cancer include the paracervical, parametrial, obturator, hypogastric, external iliac, and sacral nodes, essentially in that order. Less commonly, there is involvement in the common iliac, inguinal, and paraaortic nodes. In stage I, the pelvic nodes are positive in approximately 15% of cases and the paraaortic nodes in 6%. In stage II, pelvic nodes are positive in 28% of cases and paraaortic nodes in 16%. In stage III, pelvic nodes are positive in 47% of cases and paraaortic nodes in 28%.

Cervical cancer is still staged clinically. Physical examination, routine x-rays, barium enema, colposcopy, cystoscopy, proctosigmoidoscopy, and IVP are used to stage the disease. CT scan results, while clinically useful, are not used to stage the disease. Stage I disease is limited to the cervix. Stage Ia disease is preclinical (i.e., microscopic), while stage Ib denotes macroscopic disease. Stage II involves the vagina, but not the lower one-third, or infiltrates the parametrium but not out to the pelvic side wall. IIa denotes vaginal but not parametrial extension, while IIb denotes parametrial extension. Stage III involves the lower one-third of the vagina or extends to the pelvic side wall; there is no cancer-free area between the tumor and the pelvic wall. Stage IIIa lesions have not extended to the pelvic wall, but involve the lower one-third of the vagina. Stage IIIb tumors have extension to the pelvic wall, and/or are associated with hydronephrosis or a nonfunctioning kidney caused by tumor. Stage IV is outside the reproductive tract.

a positive IVP would mean extension to the pelvic side wall and thus a stage III carcinoma, specifically stage IIIb. Such staging applies even if there is no palpable tumor beyond the cervix.

Radical Hystrectomy involves excision of the uterus, the upper third of the vagina, the uterosacral and uterovesical ligaments, and all of the parametrium, and pelvic node dissection including the ureteral, obturator, hypogastric, and iliac nodes. Radical hysterectomy thus attempts to preserve the bladder, rectum, and ureters while excising as much as possible of the remaining tissue around the cervix that might be involved in microscopic spread of the disease. Ovarian metastases from cervical cancer are extremely rare.

·         Different tissues tolerate different doses of radiation, but the ovaries are by far the most radiosensitive. They tolerate up to 2,500 rads.

·         An important feature of the lymphatic drainage of the vulva is the existence of drainage across the midline. The vulva drains first into the superficial inguinal lymph nodes, then into the deep femoral nodes, and finally into the external iliac lymph nodes. The clinical significance of this sequence for patients with carcinoma of the vulva is that the iliac nodes are probably free of the disease if the deep femoral nodes are not involved. Unlike the lymphatic drainage from the rest of the vulva, the drainage from the clitoral region bypasses the superficial inguinal nodes and passes directly to the deep femoral nodes. Thus, while the superficial nodes usually also have metastases when the deep femoral nodes are implicated, it is possible for only the deep nodes to be involved if the carcinoma is in the midline near the clitoris.

·         Mesonephroid carcinomas tend to be associated with pelvic endometriosis.

·         Gonadoblastomas frequently contain calcifications that can be detected by plain radiography of the pelvis. Women who have gonadoblastomas often have ambiguous genitalia. The tumors are usually small, and are bilateral in one-third of affected women.

·         Mixed Müllerian tumors refer to the combination of heterologous elements—that is, tissue of different sources.

·         Uterine leiomyosarcomas are smooth muscle malignancies characterized by more than 5 mitoses per 10 hpf. These malignancies are not thought to arise from benign fibroids but occur de novo. Uterine leiomyosarcomas typically occur in postmenopausal women with a rapidly enlarging uterus.

·         Medical treatment of endometriosis currently involves a selection of four medications—oral contraceptive pills (OCPs), continuous progestins, danazol, and GnRH analogues.

Infertility & Contraception

·         The fecundability, or monthly probability of pregnancy, is 20% among fertile couples.

·         If the histologic dating of the endometrium lags 4 or more days behind the chronologic date predicted by the menstrual history, the diagnosis of luteal phase defect can be made. Clinically, these patients exhibit low serum progesterone, FSH, and LH levels.

In contrast, prolonged functioning of the corpus luteum (persistent luteal phase with continued progesterone production) results in prolonged heavy bleeding at the time of menses. Histologically, there is a combination of secretory glands mixed with proliferative glands (irregular shedding). Clinically, these patients have regular periods, but the menstrual bleeding is excessive and prolonged (lasting 10 to 14 days).

·         Pretesticular causes are those that affect the hormones that stimulate the testicles, such as a low LH or FSH. Phenytoin acts by reducing FSH. Other causes of a low LH or FSH include various hypothalamic-pituitary disorders, such as panhypopituitarism and gonadotrophin deficiency, including isolated LH deficiency and Kallmann's syndrome.

Posttesticular causes are those that affect sperm transport, and testicular causes are those with a direct effect on the testicles. Idiopathic causes represent those causes that are likely genetic and not elsewhere classified.

·         There are no diagnostic criteria for PCOS, but common findings are increased LH:FSH ratio, decreased fasting glucose:insulin ratio, polycystic ovaries on ultrasound, and obesity.

Oral contraceptives have long been used in the management of PCOS because they suppress pituitary luteinizing hormone secretion, suppress ovarian androgen secretion, and increase circulating SHBG. Medications such as metformin that improve insulin sensitivity have been used to treat PCOS. Spironolactone, which is a diuretic and aldosterone agonist, has been used to treat PCOS because it binds to the androgen receptor as an antagonist. Weight loss is recommended as part of the treatment for women with PCOS because it reduces hyperinsulinemia. Insulin is thought to act on the ovary to stimulate androgen secretion. In addition, hyperinsulinemia decreases SHBG. There is no role for the use of dexamethasone to treat PCOS.

·         DHAES is a marker of adrenal androgen production; when normal, it essentially excludes adrenal sources of hyperandrogenism.

·         Therapy with Clomiphene Citrate:

Ovulation rate: 80%

Pregnancy rate: 50%

·         OHSS is an infrequent but potentially severe complication of IVF. It is most commonly seen in young women with very high estradiol concentrations and many intermediate-sized follicles.

 OHSS usually presents 1 week after oocyte retrieval. It is characterized by ascites, weight gain, and intravascular volume depletion. In severe cases, prerenal azotemia, hemoconcentration, and a hypercoaguable state can be present.

 Treatment with aggressive hydration is indicated, even if it worsens the ascites. Paracentesis early in the course of OHSS, and repeated as needed, is often indicated.

·         IVF involves fertilizing eggs and sperm outside the body then placing embryos in the uterus.

The endometrial glandular integrin avß3 appears to be closely tied to normal uterine receptivity. It initially appears coincident with the establishment of normal uterine receptivity. avß3 expression is diminished in women suffering from endometriosis, hydrosalpinges, primary unexplained infertility, recurrent pregnancy loss, and polycystic ovarian disease. Note that strategies to optimize uterine receptivity allow for transfer of fewer embryos.

·         In anorexia nervosa, prolactin, GH, TSH, and thyroxine levels are normal, FSH and LH levels are low, and cortisol levels are elevated.

·         Müllerian agenesis, also known as MayerRokitansky-Küster-Hauser syndrome, presents as amenorrhea with absence of a vagina. The incidence is approximately 1 in 10,000 female births. The karyotype is 46,XX. There is normal development of breasts, sexual hair, ovaries, tubes, and external genitalia. There are associated skeletal (12%), urinary tract (33%) and auditory anomalies. Treatment generally consists of progressive vaginal dilation or creation of an artificial vagina with split-thickness skin grafts (McIndoe procedure).

·         Of all the medications studied, SSRIs have shown the greatest efficacy in PMS treatment.

·         Besides an increase in androgens and a moderate rise in FSH and LH levels, one of the first indications of puberty is an increase in the amplitude and frequency of nocturnal LH pulses.

·         Salpingitis isthmica nodosa, in which there is a characteristic “salt-and pepper” pattern of tubal filling and evidence of a diverticulum of the tube on one side.

·         Thyroid dysfunction and hyperprolactinemia can both be associated with hirsutism, and therefore it is important to check levels of TSH and prolactin.

·         Unintended pregnancy in women correctly using oral contraceptive pills is not related to sexual frequency, gastrointestinal disturbances, or the development of antibodies.

·         Although the incidence of ectopic pregnancies with an IUD was at one time thought to be increased, it is now recognized that in fact the overall incidence is unchanged. The apparent increase is the result of the dramatic decrease in intrauterine implantation without affecting ectopic implantation. Thus, while the overall probability of pregnancy is dramatically decreased, when a pregnancy does occur with an IUD in place, there is a higher probability that it will be an ectopic one.

·         Masters and Johnson observed a transudate-like fluid emanating from the vaginal walls during sexual response. This mucoid material, which is sufficient for complete vaginal lubrication, is produced by transudation from the venous plexus surrounding the vagina and appears seconds after the initiation of sexual excitement. No activity by Skene’s glands was noted, and production of cervical mucus during sexual stimulation was observed in only a few subjects. Fluid from Bartholin’s glands appears long after vaginal lubrication is well established; in addition, it appears to make only a minor contribution to lubrication in the late plateau phase. Uterine and tubal secretions do not contribute to this lubrication.

·         Vaginismus, defined as involuntary painful spasm of the pelvic muscles and vaginal outlet. It is usually psychogenic. It should be differentiated from frigidity, which implies lack of sexual desire, and dyspareunia, which is defined as pelvic and/or back pain or other discomfort associated with sexual activity.

·         Absolute contraindications to the use of birth control pills include (1) thromboembolic disorders [deep venous thrombosis (DVT), cerebrovascular accident (CVA), myocardial infarction (MI), or conditions predisposing to these conditions]; (2) markedly impaired liver function; (3) known or suspected carcinoma of the breast or other estrogen-dependent malignancies; (4) undiagnosed abnormal genital malignancies; (5) undiagnosed abnormal genital bleeding; (6) known or suspected bleeding; (7) known or suspected pregnancy; (8) a history of obstructive jaundice in pregnancy; (9) congenital hyperlipidemia; and (10) obesity in women who are smokers and over age 35. Relative contraindications to the use of the birth control pill require clinical judgment and informed consent. These include (1) migraine headaches; (2) hypertension; (3) uterine leiomyomas; (4) gestational diabetes; (5) elective surgery; and (6) seizure disorders.

·         Contraindications to the use of an IUD: (1) pregnancy; (2) pelvic inflammatory disease—acute, chronic, or recurrent; (3) acute cervicitis; (4) postpartum endometritis or septic abortion; (5) undiagnosed genital bleeding; (6) gynecologic malignancy; (7) congenital anomalies or uterine fibroids that distort the uterine cavity; and (8) copper allergy (for IUDs that contain copper). Other conditions that might preclude IUD insertion include (1) previous ectopic pregnancy; (2) severe cervical stenosis; (3) severe dysmenorrhea; (4) menometrorrhagia; (5) coagulopathies; and (6) congenital or valvular heart disease.

·         On occasion, following correct use of a full cycle of pills, withdrawal bleeding may fail to occur (silent menses). Pregnancy is a very unlikely explanation for this event; therefore, pills should be resumed as usual (after 7 days) just as if bleeding had occurred. However, if a second consecutive period has been missed, pregnancy should be more seriously considered and ruled out by a pregnancy test, medical examination, or both. Women occasionally forget to take pills; however, when only a single pill has been omitted, it can be taken immediately in addition to the usual pill at the usual time. This single-pill omission is associated with little if any loss in effectiveness. If three or more pills are omitted, the pill should be resumed as usual, but an additional contraceptive method (e.g., condoms) should be used through one full cycle.

·         Recent studies in animals have shown that pirfenidone, an antifibrotic agent, suppresses leiomyoma growth via its potent inhibition of fibrogenic cytokines, including basic fibroblast growth factor, platelet-derived growth factor, transforming growth factor-β, and EGF.

·         In preimplantation genetic diagnosis (PGD), a single cell or polar body is biopsied from the embryo prior to embryo transfer during an IVF cycle and subjected to genetic testing. Currently, this technique is most often used in identifying affected embryos of single gene disorders such as Gaucher disease and cystic fibrosis. With the results from testing, an unaffected embryo is transferred back into the uterus. PGD serves as an alternative to chorionic villus sampling or amnio-centesis for diagnosis and possible abortion of affected fetuses.

·         Swyer syndrome (46,XY) is characterized by a female phenotype with amenorrhea and lack of secondary sex characteristics. Growth is usually normal, and some virilization may occur after puberty, especially when gonadal tumors are present. Swyer syndrome is inherited as an X-linked recessive trait. The clinical picture without virilization and tumor propensity may also occur in 46,XX individuals. This condition is termed pure gonadal dysgenesis and is an autosomal recessive inheritance.

General Gynecology

·         Meiosis I is arrested in prOphase for years until Ovulation.

Meiosis II is arrested in METaphase until fertilization. An egg MET a sperm.

·         Relaxin is the only hormone produced both by the ovary and uterus.

Renin is the only hormone produced by both the theca and kidney.

Inhibin is produced in the granulosa, theca, and corpus luteum.

Inhibin-A under the influence of LH suppresses FSH during the luteal phase of the cycle.

Inhibin-B directly suppresses pituitary FSH secretion in the follicular phase of the cycle.

Activin is produced in the granulosa.

Follistatin is produced in follicles.

Enkephalin is produced by the ovary.

 Epidermal growth factor-like is produced in granulosa and theca.

Transforming growth factor-beta is produced in theca, ovarian interstitial tissue, and granulose.

Müllerian-inhibiting substance is produced in the granulosa.

Angiotensin II is produced in the follicular fluid.

from the granulosa: Müllerian-inhibiting substance, activin, inhibin, follicle regulatory protein, insulin-like growth factor-1, epidermal growth factor-like, platelet-derived growth factor, proopiomelanocortin, and gonadotropin surge-inhibiting factor,plasminogen activator

from the theca: transforming growth factor, renin, inhibin, and relaxin; and

from the corpus luteum: basic fibroblast growth factor,inhibin,relaxin

from follicular fluid: angiotensin II, luteinizing inhibitor and luteinizing stimulator, oocyte meiosis inhibitor, follicle regulatory protein, and renin.

·         Bacterial vaginosis is a condition is which there is an overgrowth of anaerobic bacteria in the vagina that replaces the normal lactobacillus. Women with this type of vaginitis complain of an unpleasant vaginal odor that is described as musty or fishy and a thin, gray-white vaginal discharge that is adherent to the vaginal walls. Vulvar irritation and pruritus are rarely present. To confirm the diagnosis of bacterial vaginosis, a wet smear is done. To perform a wet smear, saline is mixed with the vaginal discharge and clumps of bacteria and clue cells are identified. Clue cells are vaginal epithelial cells with clusters of bacteria adherent to their surfaces. In addition, a whiff test can be performed by mixing potassium hydroxide with the vaginal discharge. In cases of bacterial vaginosis, an amine-like odor will be detected. The treatment of choice for bacterial vaginosis is metronidazole (Flagyl) 500 mg given twice daily for 7 days.

·         In cases of candidiasis, patients commonly complain of vulvar burning, pain, pruritus, and erythema. The vaginal discharge tends to be white, highly viscous, granular, and adherent to the vaginal walls. A wet smear with potassium hydroxide can confirm the diagnosis by the identification of hyphae. Treatment of candidiasis can achieved with the administration of topical imidazoles or triazoles or the oral medication Diflucan.

·         Trichomonas vaginitis is the most common nonviral, nonchlamydial sexually transmitted disease of women. It is caused by the anaerobic, flagellated protozoan T. vaginalis. Women with Trichomonas vaginitis commonly complain of a copious vaginal discharge that may be white, yellow, green, or gray and that has an unpleasant odor. Some women complain of vulvar pruritus, which is primarily confined to the vestibule and labia minora. On physical exam, the vulva and vagina frequently appear red and swollen. Only a small percentage of women possess the classically described strawberry cervix. Diagnosis of trichomoniasis is confirmed with a wet saline smear. Under the microscope, the Trichomonas organisms can be visualized under high power; these organisms are unicellular protozoans that are spherical in shape with three to five flagella extending from one end. The recommended treatment for trichomoniasis is a one-time dose of 2 g metronidazole.

·         Chlamydia trachomatis is an intracellular parasite that can cause an infection that may be manifested as cervicitis, urethritis, or salpingitis. Patients with mild cases may be asymptomatic. On physical exam, women with chlamydial infections may demonstrate a mucopurulent cervicitis. The diagnosis of chlamydia is suspected on clinical exam and confirmed with cervical cultures. Treatment for a chlamydial cervicitis is with oral azithromycin, 1 g, or doxycycline 100 mg twice daily for 7 days.

·         Treatment of Bartholin's cysts with marsupialization has the best success rate.

Although rare, adenocarcinoma of the Bartholin’s gland must be excluded in women over 40 years of age who present with a cystic or solid mass in this area. The appropriate treatment in these cases is surgical excision of the Bartholin’s gland to allow for a careful pathologic examination. In cases of abscess formation, both marsupialization of the sac and incision with drainage as well as appropriate antibiotics are accepted modes of therapy. In the case of the asymptomatic Bartholin’s cyst, no treatment is necessary.

·         The classic physical exam finding of PID is the "chandelier sign," which describes the patient's response to severe pain caused by movement of the cervix.

·         In the female, the order of puberty is thelarche (breast bud), pubarche (pubic hair), maximum growth velocity, and menarche.

·         The two syndromes that are characterized by breast development and absence of a uterus, androgen insensitivity and müllerian agenesis, can be distinguished by a karyotype.

·         Ferriman and Gallwey Scoring system for scoring hirsutism depending on body site. Less than 8 is normal; greater than 15 is severe.

·         The two main types of specula commonly used to perform Pap smears are the Pederson and Graves specula. The Pederson speculum works best for nulliparous women and menopausal women with atrophic vaginas; the blades are flat and narrow and barely curve on the sides. The blades of the Graves speculum are wider, higher, and curved on the sides; they work better for parous women with looser vaginal walls. A child’s vagina can best be examined using an instrument called a vaginoscope or some type of endoscope such as a hysteroscope. The Graves and Pederson speculums come in pediatric sizes to be used in virginal adults or young children.

·         Vulvar vestibulitis is syndrome of unknown etiology. To make the diagnosis of this disorder, the following three findings must be present: (1) severe pain on vestibular touch or attempted vaginal entry, (2) tenderness to pressure localized within the vulvar vestibule, and (3) visible findings confined to vulvar erythema of various degrees. To treat vulvar vestibulitis, the first step is to avoid tight clothing, tampons, hot tubs, and soaps, which can all act as vulvar irritants. Topical treatments include lidocaine, estrogen, and steroids. Tricyclic antidepressants and intralesional interferon injections have also been used. For women refractory to medical therapy, surgical excision of the vestibular mucosa may be helpful.

·         The Centers for Disease Control’s recommendation for inpatient management of PID includes the following:

1. Cefoxitin 2 g IV every 6 h or cefotetan 2 g IV every 12 h plus doxycycline 100 mg PO or IV twice daily or
2. Clindamycin 900 mg IV every 8 h plus gentamicin loading dose IV or IM (2 mg/kg) followed by maintenance dose (1.5 mg/kg) every 8 h

The Centers for Disease Control’s recommendation for the outpatient management of PID includes the following:

1. Cefoxitin 2 g IM plus probenecid 1 g PO in a single dose concurrently or ceftriaxone 250 mg IM plus doxycycline 100 mg PO twice daily for 14 days or
2. Ofloxacin 400 mg PO two times a day for 14 days plus either clindamycin 450 mg PO four times a day or metronidazole 500 mg PO two times a day for 14 days.