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.