INFERTILTY

BY HUSSEIN TALAL SABBAN

• Infertility: is the failure to conceive (regardless of cause)

after 1 year of unprotected intercourse.• Infertility affects approximately 10-15% of

reproductive-aged couples.

• Fertility : is defined as the capacity to reproduce or the

state of being fertile. • fecundability: is the probability of achieving a pregnancy each

month • Fecundity: is the ability to achieve a live birth within 1

menstrual cycle

Etiology of Infertility

• Reproduction requires the interaction and integrity of the female and male reproductive tracts, which involves:

(1) the release of a normal preovulatory oocyte. (2) the production of adequate spermatozoa.

(3) the normal transport of the gametes to the ampullary portion of the fallopian tube (where fertilization occurs)

(4) the subsequent transport of the cleaving embryo into the endometrial cavity for implantation and development.

• Infertility is caused by male and/or female factors.

• Male and female factors each account for approximately 35% of cases.

• Often, there is more than one factor, with male and female factors combined causing 20% of infertility.

• In the remaining 10% of cases, the etiology is unknown.

Female Factor Infertility

• Female factor infertility can be divided into several categories:

• cervical• uterine• ovarian• tubal • other

• Cervical factor infertility:

• Cervical factor infertility can be caused by stenosis or abnormalities of the mucus-sperm interaction. The uterine cervix plays a pivotal role in the transport and capacitation of the sperm after intercourse. Cervical factors account for 5-10% of infertility

• Uterine factor infertility:

• The uterus is the final destination for the embryo and the place where the fetus develops until delivery. Therefore, uterine factors may be associated with primary infertility or with pregnancy wastage and premature delivery. Uterine factors can be congenital or acquired. They may affect the endometrium or myometrium and are responsible for 2-5% of infertility cases.

• Ovarian factor infertility:

• Ovulatory dysfunction is defined as an alteration in the frequency and duration of the menstrual cycle. A normal menstrual cycle lasts 25-35 days, with an average of 28 days. Failure to ovulate is the most common infertility problem. Absence of ovulation can be associated with primary amenorrhea, secondary amenorrhea, or oligomenorrhea.

• Advanced age:

• The prevalence of infertility rises dramatically as age increases.7

Furthermore, fertility decreases with marriage duration because of less frequent intercourse and/or the use of contraception.

• Tubal factors:• Abnormalities or damage to the fallopian tube interferes with

fertility and is responsible for abnormal implantation (eg, ectopic pregnancy). Obstruction of the distal end of the fallopian tubes results in accumulation of the normally secreted tubal fluid, creating distention of the tube with subsequent damage of the epithelial cilia (hydrosalpinx).

• Other tubal factors associated with infertility are either congenital or acquired. Congenital absence of the fallopian tubes can be due to spontaneous torsion in utero followed by necrosis and reabsorption. Elective tubal ligation and salpingectomy are acquired causes.

• Peritoneal factors:• The uterus, ovaries, and fallopian tubes share the same space within the

peritoneal cavity. • Anatomical defects or physiologic dysfunctions of the peritoneal cavity,

including infection, adhesions, and adnexal masses, may cause infertility. • Pelvic inflammatory disease, peritoneal adhesions secondary to previous

pelvic surgery, endometriosis, and ovarian cyst rupture all compromise the motility of the fallopian tubes or produce blockage of the fimbriae with development of hydrosalpinx.

• Large myomas, pelvic masses, or blockage of the cul-de-sac interferes with the accumulation of peritoneal fluid and interferes with the normal oocyte pickup mechanism.

• Peri-ovarian adhesions that encapsulate the ovary interfere with the normal oocyte release at ovulation, becoming a mechanical factor for infertility.

• Male Factor Infertility:• Male factor infertility can be divided into pretesticular,

testicular, and posttesticular etiologies. • Factors Affecting Both Sexes• Environmental and occupational factors• Concern regarding the impact of environmental factors

on fertility is increasing. Published semen analysis reports from 1985 confirm a 20% decrease of sperm concentration compared with reports published in the 1960s.Toxic effects related to tobacco, marijuana, and other drugs

General Guidance on Evaluation of Infertility

• History• The couple should provide a copy of their previous medical records and

complete a medical history questionnaire• Obtain a detailed medical history regarding the type of infertility (primary

or secondary) and its duration.• Obtain a history of previous pregnancies and their outcomes; interval

between pregnancies; and detailed information about pregnancy loss, duration of pregnancy, human chorionic gonadotropin (hCG) level, ultrasonographic data, and the presence or absence of a fetal heartbeat.

• During the history of previous infertility evaluation and treatment, specific questions should address the issues of frequency of intercourse, use of lubricants (eg, K-Y gel) that could be spermicidal, use of vaginal douches after intercourse, and the presence of any sexual dysfunction such as anorgasmia or dyspareunia.

• Question female patients about their menstrual history, frequency, and patterns since menarche. A history of weight changes, hirsutism, frontal balding, and acne should also be addressed.

• Ask male patients about previous semen analysis results, history of impotence, premature ejaculation, change in libido, history of testicular trauma, previous relationships, history of any previous pregnancy, and the existence of offspring from previous partners.

• Ask the couple about their history of sexually transmitted diseases (STDs); surgical contraception (eg, vasectomy, tubal ligation); lifestyle; consumption of alcohol, tobacco, and recreational drugs (amount and frequency); occupation; and physical activities.

• Ask the couple whether they are currently under medical treatment, the reason, and whether they have a history of allergies.

• A complete review of systems may be helpful to identify any endocrinological or immunological problem that may be associated with infertility.

• Physical• A physical examination should be completed if one has not

been recently performed by a gynecologist. • Measure height and weight to calculate the body mass

index, and measure arm span when indicated.• Perform an eye examination to establish the presence of

exophthalmos, which can be associated with hyperthyroidism.

• The presence of epicanthus, lower implantation of the ears and hairline, and webbed neck can be associated with chromosomic abnormalities.

• Carefully evaluate the thyroid gland to exclude gland enlargement or thyroid nodules.

• Perform a breast examination to evaluate breast development and to seek abnormal masses or secretions, especially galactorrhea

• The abdominal examination should be directed to the presence of abnormal masses at the hypogastrium level.

• A thorough gynecologic examination should include an evaluation of hair distribution, clitoris size, Bartholin glands, labia majora and minora, and any condylomata acuminatum or other lesions that could indicate the existence of venereal disease.– The inspection of the vaginal mucosa may indicate a

deficiency of estrogens or the presence of infection.– The evaluation of the cervix should include a

Papanicolaou test and cultures for gonorrhea, chlamydia, Ureaplasma urealyticum, and Mycoplasma hominis.

• Bimanual examination should be performed to establish the direction of the cervix and the size and position of the uterus to exclude the presence of uterine fibroids, adnexal masses, tenderness, or pelvic nodules indicative of infection or endometriosis.

• The examination of the extremities is important to rule out malformation, such as shortness of the fourth finger or cubitus valgus, which can be associated with chromosomal abnormalities and other congenital defects. Examine the skin to establish the presence of acne, hypertrichosis, and hirsutism.

• The urologist usually examines the male partner if the patient's history of his semen analysis produces an abnormal finding.– Attention should be directed to congenital abnormalities of

the genital tract (eg, hypospadias, cryptorchid, congenital absence of the vas deferens).

– Testicular size, urethral stenosis, and presence of varicocele are also determined.

– A history of previous inguinal hernia repair can indicate an accidental ligation of the spermatic artery.

Comprehensive Evaluation of Infertility

• Evaluation of infertile couples should be organized and thorough.

• Diagnostic tests should progress from the simplest (eg, pelvic ultrasonography) to the more complex and invasive (eg, laparoscopy).

• The couple may be stressed by their need to seek medical intervention; therefore, to relieve anxiety, emphasize that a complete infertility evaluation is performed according to the woman's menstrual cycle and may take up to 2 menstrual cycles before the etiology is determined

Cervical factors The postcoital test (PCT Cervical stenosis can be diagnosed during a speculum

examination.Uterine factors pelvic examination HSG, pelvic ultrasonography, hysterosonogram, and MRI. Operative procedures such as laparoscopy and hysteroscopy

are often necessary for confirmation of the final diagnosis. Tubal and peritoneal factors The 2 most frequent tests used for diagnosis of tubal

pathology are laparoscopy and hysterosalpingogram.

• Ovarian factors Ovulation

– Ovulation is usually inferred when a woman reports regular cycles. If there is doubt, a progesterone greater than 4 ng/mL is indicative of ovulation. Sonographic confirmation of follicle rupture with serial ultrasonography can also be performed.

– Basal body temperature charts can be used to predict ovulation• Ovarian reserve

– The level of ovarian reserve and the age of the female partner are the most important prognostic factors in the fertility workup.

– Ovarian reserve is most commonly evaluated by checking a cycle day 3 FSH and estradiol level. Normal ovarian function is indicated when the FSH level is less than 10 mIU/mL and the estradiol level is less than 65 pg/mL

• Since thyroid disease and hyperprolactinemia can cause menstrual abnormalities and infertility, a serum TSH and prolactin should always be checked and corrected prior to

• Evaluation of the Male Partner: The male partner must submit a semen sample for a

comprehensive semen analysis. Previous paternity does not guarantee current fertility status.

• Sperm function tests (1) the acrosome reaction test with fluorescent lectins or

antibodies. (2) computer assessment of the sperm head (3) computer motility assessment (4) hemizona-binding assay (5) hamster penetration test (6) human sperm-zona penetration assay