Infertility Flashcards
Define:
Infertility
1. Primary Infertility
2. Secondary Infertility
3. Fecundability
4. Fecundity
5. Incidence
DEFINITION
Infertility is defined as the inability to conceive within one or more years of regular unprotected coitus.
Primary infertility denotes those patients who have never conceived. Secondary infertility indicates previous pregnancy but failure to conceive subsequently.
Fecundability is defined as the probability of achieving a pregnancy within one menstrual cycle. In a healthy young couple, it is 20%.
Fecundity is the probability of achieving a live birth within a single cycle.
- Factors essential for Conception?
- Physiological Consideration for Infertility?
- Incidenceof Infertility?
Factors Essential for Conception
■Healthy spermatozoa should be deposited high in the vagina at or near the cervix (male factor).
■ The spermatozoa should undergo changes (capaci- tation, acrosome reaction) and acquire motility (cervical factor).
■The motile spermatozoa should ascend through the cervix into the uterine cavity and the fallopian tubes.
■There should be ovulation (ovarian factor).
■The fallopian tubes should be patent and the oocyte should be picked up by the fimbriated end of the tube (tubal factor).
■The spermatozoa should fertilize the oocyte at the ampulla of the tube.
The embryo should reach the uterine cavity after 3-4 days of fertilization.
The endometrium should be receptive [by estrogen, progesterone, insulin-like growth factor-1 (IGF-1), cytokines, integrins] for implantation, and the corpus luteum should function adequately.
INCIDENCE
About 80% of the couples achieve conception if they so desire, within one year of having regular intercourse with adequate frequency (4-5 times a week). Another 10% will achieve the objective by the end of second year. As such, 10% remain infertile by the end of second year.
Causes of Infertility
Areas of Infertility?
Physiology of Spermatogenesis?
Common causes of Male Infertility?
Obstruction of Efferent duct seen in?
Causes of Failure to deposit sperm high in vagina ?
What are the Errors in Seminal fluid?
What are the causes of Semen abnormalities?
CAUSES OF INFERTILITY
Conception depends on the fertility potential of both the male and female partner. The male is directly responsible in about 30-40%, the female in about 40-55% and both are responsible in about 10% cases. The remaining 10% is unexplained, in spite of thorough investigations with modern technical know-how. It is also strange that 4 out of 10 patients of unexplained category become pregnant within 3 years without having any specific treatment.
It is also emphasized that the relative subfertility of one partner may sometimes be counterbalanced by the high fertility of the other.
Areas of Male Infertility (Table 17.1)
■Defective spermatogenesis
■ Obstruction of the efferent duct system
Failure to deposit sperm high in the vagina
Errors in the seminal fluid.
Physiology of Spermatogenesis
Follicle-stimulating hormone (FSH) stimulates sperma- togenesis from basal cells of the seminiferous tubules. Sertoli cells envelope the germ cells and support sper matogenesis. Sertoli cell function is controlled by FSH and testosterone. Scrotal temperature should be 1-2°F less than the body temperature. Luteinizing hormone (LH) is required for the synthesis of testosterone from the Leydig cells. FSH also stimulates the Sertoli cells to produce androgen binding proteins (ABP) and inhibin B. ABP binds to testosterone and dihydrotestosterone to maintain the local high concentration of androgens. Spermatogenesis and sperm maturation need a high androgenic environ- ment. Inhibin B inhibits FSH secretion. Spermatogenesis is controlled predominantly by the genes on Y chromo- some. Approximately 74 days are required to complete the process of spermatogenesis. Additional 12-20 days are needed for spermatozoa to travel the epididymis.
Common causes of male infertility
The important causes are: (a) Hypothalamic-pituitary disorders (1-2%); (b) Primary testicular disorders (30-40%); (c) Disorders of sperm transport (10-20%); (d) Idiopathic (40-50%).
■ Congenital:
Undescended testes: The hormone secretion remains unaffected, but the spermatogenesis is depressed. Vas deferens is absent (bilateral) in about 1-2% of infertile males.
• Kartagener syndrome (autosomal disease)-there is loss of ciliary function and sperm motility.
• Hypospadias causes failure to deposit sperm high in vagina.
■Thermal factor: The scrotal temperature is raised in
conditions such varicocele. Varicocele probably interferes with the cooling mechanism or increases catecholamine concentration. However, no definite association between varicoceles and infertility has been established.
Infection: (a) Mumps orchitis after puberty_may permanently damage spermatogenesis; (b) The quality of the sperm is adversely affected by chronic systemic illness like bronchiectasis. Bacterial or viral infection of the seminal vesicle or prostate depresses the sperm count; (c) T. mycoplasma or Chlamydia trachomatis infection is also implicated.
■ General factors: Chronic debilitating diseases, mal- nutrition or heavy smoking reduce spermatogenesis. Alcohol inhibits spermatogenesis either by suppressing Leydig cell synthesis of testosterone or possibly by sup- pressing gonadotropin levels.
■ Endocrine: Testicular failure due to gonadotro- pin deficiency (Kallmann’s syndrome) is rare. FSH level is raised in idiopathic testicular failure with germ cell hypoplasia (Sertoli-cell-only-syndrome).
Hyperprolactinemia is associated with impotence.
■ Genetic: Common chromosomal abnormality in azoospermic male is Klinefelter’s syndrome (47 XXY). Gene microdeletion have been detected in the long- arm of Y chromosome (Yq) for patients with severe oligospermia and azoospermia. Nearly 80% of men with congenital bilateral absence of vas deferens (CBAVD) have genetic mutations. About 66% of men with cystic fibrosis have CBAVD.
■Iatrogenic: Radiation, cytotoxic drugs, nitrofurantoin, cimetidine, ẞ blockers, antihypertensive, anticonvul- sant, and antidepressant drugs are likely to hinder spermatogenesis.
■Immunological factor: Antibodies against spermato-
zoal surface antigens may be the cause of infertility. This results in clumping of the spermatozoa after ejaculation.
Obstruction of the Efferent Ducts
The efferent ducts may be obstructed by infection like tubercular, gonococcal or by surgical trauma (hernior- rhaphy) following vasectomy. In Young’s syndrome, there is epididymal obstruction and bronchiectasis.
Failure to Deposit Sperm High in the Vagina (Coital Problems)
■Erectile dysfunction
■Ejaculatory defect-premature, retrograde or absence of ejaculation
■
Hypospadias.
Sperm abnormality: Loss of sperm motility (asthenozoo- spermia), abnormal sperm morphology (roundheaded sperm, teratozoospermia) are the important factors..
Errors in the Seminal Fluid
■Unusually high or low volume of ejaculate
■No ejaculate: Ductal obstruction, retrograde ejacula- tion, hypogonadism
■Low volume: Absence of seminal vesicles, infection, ductal obstruction
■Abnormal viscocity: Cause unknown.
Causes of Semen Abnormalities
■ Azoospermia: Klinefelter’s syndrome, Sertoli cell only syndrome, agenesis of seminiferous tubules, hypogonadotropic hypogonadism, Young syndrome.
■ Oligozoospermia: Genetic disorder, endocrinopathies, maturation arrest, exogenous factors.
■Abnormal motility: Immunologic factors, infection, varicocele, sperm structural defects, metabolic abnormalities.
- Causes of Female Infertility? (FIGO]
- Ovarian Factors responsible for Infertility?
- Tubal factors?
- Uterine Factors?
- Cervical Factors?
- Vaginal Factors?
- Combined factors?
CAUSES OF FEMALE INFERTILITY (FIGO) (FIG. 17.1)
Ovulatory dysfunction: 30-40%
Tubal disease: 25-35%
Uterine factors: 10%
Cervical factors: 5%
Pelvic endometriosis: 1-10%.
Ovarian Factors
The ovulatory dysfunctions (dysovulatory) are:
■Anovulation or oligo-ovulation
Decreased ovarian reserve
■Luteal phase defect (LPD)
■Luteinized unruptured follicle (LUF)
Anovulation or oligo-ovulation
The ovarian activity is totally dependent on the gonadotro- pins and the normal secretion of gonadotropins depends on the pulsatile release of GnRH from hypothalamus. As such, ovarian dysfunction is likely to be linked with disturbed hypothalamo-pituitary-ovarian axis either primary or secondary from thyroid or adrenal dysfunc- tion.
Thus, the disturbance may result not only in ano- vulation but may also produce oligomenorrhea or even amenorrhea. Other causes of anovulation are: Polycystic ovarian syndrome, elderly women and women with premature ovarian failure (p. 389). Possible causes of anovulation are given schematically (Fig. 17.1).
As there is no ovulation, there is no corpus luteum formation. In the absence of progesterone, there is no secretory endometrium in the second half of the cycle. The other features of ovulation (later in the Ch.) are absent.
Luteal phase defect (LPD)
In this condition, there is inadequate growth and function of the corpus luteum. There is inadequate progesterone secretion. The lifespan of corpus luteum is shortened to less than 10 days. As a result, there is inadequate secretory changes in the endometrium which hinder implantation. LPD is due to defective folliculogenesis which again may be due to varied reasons. Drug-induced ovulation, decreased level of FSH and/or LH, elevated prolactin, subclinical hypothyroidism, older women, pelvic endometriosis, dysfunctional uterine bleeding are the important causes.
Luteinized unruptured follicular syndrome (trapped ovum)
In this condition, the ovum is trapped inside the follicle, which gets luteinized. The cause is obscure but may be associated with pelvic endometriosis or with hyperprolactinemia.
Resistant ovarian syndrome: The follicles are present but FSH receptor is either absent or resistant.
Tubal Factors
Tubal and peritoneal factors are responsible for about 30-40% cases of female infertility.
The obstruction of the tubes may be due to (a) Pelvic infections causing: (i) Peritubal adhesions, (ii) Endosalpingeal damage; (b) Previous tubal surgery or sterilization; (c) Salpingitis isthmica nodosa (p. 114); (d) Tubal endometriosis and others; (e) Polyps or mucous debris within the tubal lumen; (f) Tubal spasm.
Common infections are: Chlamydia and gonococcus, tuberculosis (postabortal or puerperal).
Peritoneal factors: In addition to peritubal adhesions, even minimal endometriosis may produce infertility. Deep dyspareunia too often troubles the patient. The possible multifactorial mechanisms which operate in minimal endometriosis are depicted schematically at Table 17.2.
Uterine Factors
The endometrium must be sufficiently receptive enough for effective nidation and growth of the fertilized ovum. The possible factors that hinder nidation are uterine hypoplasia, inadequate secretory endometrium, fibroid uterus, endometriosis, endometritis (tubercular in par- ticular), uterine synechiae or congenital malformation of uterus.
Cervical Factors
Anatomic: Anatomic defects preventing sperm ascent may be due to congenital elongation of the cervix and second degree uterine prolapse.
Physiologic: The cervical mucus may be scanty following amputation, conization or deep cauterization of the cervix. Presence of antisperm or sperm immobilizing antibodies may be implicated as immunological factor of infertility.
Vaginal Factors
Atresia of vagina (partial or complete), transverse vaginal septum, septate vagina, or narrow introitus causing dyspare- unia are included in the congenital group. Dyspareunia may be the real problem in such cases.
Combined Factors
■Presence of factors both in the male and female partners causing infertility.
General factors: Advanced age of the wife beyond 35 years is related but male spermatogenesis continues throughout life although aging reduces the fertility in male also.
■Infrequent intercourse
Apareunia and dyspareunia (p. 470).
Anxiety and apprehension.
Use of lubricants during intercourse, which may be spermicidal.
Immunological factors.
Possible mechanisms of subinfertility in women with Pelvic Endometriosis?
Investigations of Infertility?
1. Objectives of investigation
2. Clinical approach to Investigations
Male
History
Examination
Investigations
Collection
Normal male fertility findings?
In depth evaluation for the male done in?
Semen analysis (WHO-2010)
Objectives of Investigation
■To detect the etiological factor(s)
■To rectify the abnormality in an attempt to improve the fertility
■To give assurance with explanation to the couple if no
abnormality is detected.
When to investigate? As per the definition, the infertile couple should be investigated after one year of regular unprotected intercourse with adequate frequency. The interval is however, shortened to 6 months after the age of 35 years of the woman and 40 years of the man.
- What to investigate? The basic investigations to be carried out are: (a) Semen analysis; (b) Confirmation of ovulation; (c) Confirmation of tubal patency.
It is important that both partners should come at the first visit. Detailed general and reproductive history should be taken in pr presence of both. However, the clinical examination of each partner is carried out separately.
Clinical Approach to Investigations
■Male
■Female
Male
History
■Age
■Duration of marriage
■Contraception used
■History of previous marriage
■Sexual dysfunction
■Anosmia
A general medical history should be taken with special reference to family history, durgs, history of chemotherapy durgs, radiotherapy, sexually transmitted diseases: (a) Mumps orchitis after puberty; (b) Diabetes; (c) Recurrent chest infection; (d) Bronchiectasis. Enquiry about relevant surgery such as herniorrhaphy, operation on testes, also about the sexual history, erectile dysfunction, social habits, particularly heavy smoking or alcohol.
Examination
A thorough physical examination is performed to determine the general state of health. This includes: Body mass index (BMI), hair, growth and gynecomastia inspection and an, hair, and should be paid to the size and consistency of the testicles. Testicular volume (measured by an orchidometer) should be at least 20 mL. Presence of varicocele should be elicited in the upright position.
Investigations
■Routine investigations include urine and blood examination including postprandial sugar.
■Semen analysis: This should be the first step in investigation because, if some gross abnormalities are detected (e.g. azoospermia), the couple should be counseled for the need of assisted reproductive technology.
Collection
The collection is best done by masturbation, failing which by coitus interruptus. The semen is collected in a clean wide mouthed dry glass jar. The sample so collected should be sent to the laboratory as soon as possible so that the examination can be performed within 2 hours. Sperm motility begins to decline 2 hours after ejaculation. The coitus should be avoided for 2-3 days prior to the test (abstinence).
In selected cases, biochemical tests of creatine phosphokinase and reactive oxygen species are done as sperm function tests. Creatinine phosphokinase helps sperm tuansport while reactive oxygen species and the peroxides interfere with sperm function.
Normal male fertility requires a count of over 15 million spermatozoa per ml and a progressive motility of over 32%. Semen values normally vary widely. Two properly performed semen analysis at least 4 weeks apart should be done when one report is abnormal.
In-depth evaluation for the male
These are needed in cases of (a) Azoospermia; (b) Oligospermia; (c) Low volume ejaculate; (d) Problems of sexual potency. Further diagnostic protocols has been appropriately designed.
■Serum FSH, LH, testosterone, prolactin, and TSH: Testicular dysfunction causes rise in FSH and LH. Low level of FSH and LH suggest hypogonadotropic hypogonadism (Flowchart 17.1). Leydig cell dysfunction causes low testosterone and high LH level. Elevated prolactin due to pituitary adenoma may cause impotency.
Testicular biopsy: Either open or percutaneous testicular biopsy is done to differentiate primary testicular failure from obstructive cause of azoospermia or severe oligospermia. Men with elevated serum FSH, may have adequate sperm on biopsy for use in intracytoplasmic sperm injection (ICSI). The biopsy specimen may be cryopreserved for future use in IVF/ICSI cycle. Thus testicular biopsy may have diagnostic prognostic and therapeutic value.
■ Karyotyping and genetic testing: Abnormal karyotype has been observed in men suffering from azoospermia (15%) and severely oligospermia (5%). Genetic abnormalities have health risks of patient and the offsprings. Men with sperm concentration between 3 and 10 million/mL are considered for karyotyping and genetic testing. Klinefelter syndrome (47, XXY) are seen 1 in 500 men. Nearly 15% of men with severe oligospermia or azoospermia, will have microdeletion of the Y chromosome. These deletions are inherited by their offspring.
■ Immunological tests: Two types of antibodies have been described-sperm agglutinating and sperm immobilizing; the latter is probably related to infertility. The antibodies are produced following infection (orchitis), trauma or vasectomy. These antibodies can be detected from the serum by the sperm immobilizing test. Presence of sperm antibodies in the cervical mucus is demonstrated by postcoital test.
■ Presence of plenty of pus cells requires prostatic massage. The collected fluid is to be examined by staining and culture to detect the organisms and appropriate antibiotic sensitivity.
Aspermia
Hypospermia
Oligospermia/Oligozoospermia
Polyzoospermia
Azoospermia
Asthenozoospermia
Necrozoospermia
Teratozoospermia
Oligo asthenoteratozoospermia?
Investigation protocol for male factors of Infertility
NOMENCLATURE
• Aspermia: Failure of emission of semen (no ejaculate).
• Hypospermia: Low semen volume (<2 mL).
• Oligospermia/oligozoospermia: Sperm count is less than 20 million per mL.
• Polyzoospermia: Count is more than 350 million/mL. Azoospermia: No spermatozoan in the semen.
+ Asthenozoospermia: Reduced sperm motility. Leukocy-
tospermia: Increased white cells in semen.
• Necrozoospermia: Spermatozoa are dead or motionless. Teratozoospermia: >70% spermatozoa with abnormal morphology.
◆ Oligoasthenoteratozoospermia: Disturbance of all 3 variables.
Clinical approach to Female Infertility?
History
Examinations?
Special Investigations?
Female History
Age, duration of marriage, history of previous marriage with proven fertility if any, are to be noted.
■ A general medical history should be taken with special reference to tuberculosis, sexually transmitted infections, features suggestive of pelvic inflammation or diabetes.
■ The surgical history should be directed especially towards abdominal or pelvic surgery.
■ Menstrual history should be taken in details. Wide spectrum of abnormalities ranging from hypomenor- rhea, oligomenorrhea to amenorrhea are associated with disturbed hypothalamo-pituitary ovarian axis. This may be either primary or secondary to adrenal or thy- roid dysfunction.
■ Previous obstetric history: In a case of secondary infer- tility history of postabortal or puerperal sepsis may be responsible for ascending infection and tubal damage.
Uterine synechiae may be due to vigorous curettage.
■ Contraceptive practice should be elicited. IUCD use may cause PID.
■ Sexual problems such as dyspareunia, and loss of libido are to be enquired.
Examinations
■ General, systemic and gynecological examinations are made to detect any abnormality which may hinder fertility.
■ General examination must be thorough-special emphasis being given to obesity or marked reduction in weight (BMI). Hirsutism, acne, acanthosis nigricans or underdevelopment of secondary sex characters are to be noted. Physical features pertaining to endocrinopathies are carefully evaluated to detect features of polycystic ovary syndrome (PCOS) and galactorrhea.
■ Systemic examination may accidentally detect such abnormalities like hypertension, organic heart disease, thyroid dysfunction, and other endocrinopathies.
■ Gynecological examination includes adequacy of hymenal opening, evidences of vaginal infections (C. trachomatis, Mycoplasma), uterine size, position and mobility, presence of unilateral or bilateral adnexal masses-tenderness and presence of nodules in the pouch of Douglas (POD).
■Speculum examination may reveal abnormal cervical discharge. The discharge is to be collected for Gram stain and culture. Cervical smear is taken as a screening procedure as a routine or in suspected cases.
Special investigations
Couple counseling is essential before initiation of treatment. The couple is informed about the need of evaluation for both the partners, diagnostic tests, time, needed the cost of treatment and the probable outcome.
The following guidelines are to be followed:
■In the presence of major fault in male such as azoospermia due to testicular destruction or intersex, there is very little scope to proceed for investigation for the female partner. However, considering the place of assisted reproductive technology (ART) female investigation may not be withheld.
■Similarly, when a major defect is detected in female such as Müllerian agenesis or intersex, infertility investigations should be suspended till the basic pathology is treated.
■Noninvasive or minimal invasive methods are to be employed prior to major invasive one.
■Detection of abnormality-multiple defects may be present in the same case, e.g. tubal defects may be associated with anovulation.
■Pregnancy following laparoscopy and dye test or hys- terosalpingography is not uncommon. It is presumed that small flimsy adhesions or any mucus plug obstruct- ing the tubal lumen is removed during such procedures.
■ Genital tuberculosis as a cause of infertility is to be kept in mind especially in the developing countries. The association is as high as 10-15% in contrast to a low figure of 0.5% in the developed countries.
■Use of ultrasonography: Ultrasonography (TVS) is helpful to detect pathologies like fibroids, endometrio- sis, PCOS, or tubo-ovarian mass. Antral follicular count (AFC) can be done to assess the ovarian reserve similar to that of anti-Müllerian hormone AMH. AFC is done on cycle D1 to D4. Ovarian AFC is a reliable predictor of the response to ovulation induction. Antral follicles between 2 and 10 mm are counted in both the ovaries. A count <10 (normal (0-20) predicts poor response to gonadotropin stimulation.
Investigations of Female Partner
a) Diagnosis of Ovulation
b) Diagnosis of Tubal and peritoneal factors
c) Diagnosis of Uterine Pathology
d) Diagnosis of Cervical Pathology
Investigations of the Female Partner
(A) Diagnosis of ovulation (Table 17.4); (B) Diagnosis of tubal and peritoneal factors; (C) Diagnosis of uterine pathology; (D) Diagnosis of cervical pathology.
Ovarian factors: Ovarian dysfunctions (dysovulatory)
commonly associated with infertility are:
■Anovulation or oligo-ovulation (infrequent ovulation).
■Luteal phase defect (LPD).
■Luteinized unruptured follicle (LUF).
Diagnosis of Ovulation
The various methods used in practice to detect ovulation are grouped as follows (Table 17.4):
■ Indirect
■Direct
■ Conclusive
Indirect
The indirect or presumptive evidences of ovulation are commonly used in clinical practice. These are inferred from:
■Menstrual history
■ Evaluation of peripheral or endorgan changes due to estrogen and progesterone
■Direct assays of gonadotropins or steroid hormones preceding, coinciding or succeeding the ovulatory process.
Menstrual history
The following features in relation to menstruation are
strong evidences of ovulation.
Regular normal menstrual loss between the age of 20-35.
■Midmenstrual bleeding (spotting) or pain or excessive mucoid vaginal discharge (Mittelschmerz syndrome).
■Features suggestive of premenstrual syndrome or primary dysmenorrhea.
Evaluation of peripheral or endorgan changes
(Table 17.4) Basal body temperature (BBT)
Observation: There is “biphasic pattern” of temperature variation in ovulatory cycle. If pregnancy occurs, the rise of temperature sustains along with absence of the period. In anovulatory cycle, there is no rise of temperature throughout the cycle (monophasic).
Principle
The rise of temperature is secondary to rise in serum progesterone following ovulation. Progesterone is ther- mogenic. The primary reason for the rise is the increase in the production and secretion of norepinephrine which is also thermogenic.
Procedures: The patient is instructed to take her oral temperature daily on waking up in the morning before rising out of the bed. The temperature is recorded on a special chart.
Interpretation: The body temperature is raised to
0.5-1°F (0.2-0.5°C) following ovulation. The rise sustains throughout the second half of the cycle and is called “biphasic pattern” (Fig. 17.2). There may be a drop in the temperature to about 0.5°F before the rise and almost coincides with either LH surge or ovulation. The demonstrable rise actually occurs about 2 days after the LH peak and with a peripheral level of progesterone greater than 5 ng/mL. Optimally timed intercourse during the fertile period increases the chance of conception (20%). “Biphasic temperature” pattern suggests ovulation. Measurement of LH by urinary immunoassays is superior to BBT in determining the optimal time of intercourse or insemination (IUI).
Clinical importance: It helps the couple to determine the most fertile period, if the cycle is irregular.
Limitations of BBT
■BBT indicates ovulation retrospectively
■It cannot predict ovulation precisely with time
■Ovulation may occur over a span of several days in the thermogenic phase
■Rarely, ovulation has been observed though BBT is monophasic.
Cervical mucus study: Disappearance of fern after 22nd day of the cycle is suggestive of ovulation. Persistence of fern pattern even beyond 22nd day suggests anovulation.
Progesterone causes dissolution of the sodium chloride crystals. Following ovulation, there is loss of stretchability (spinnbarkeit), which was present in the midcycle (p. 93).
Vaginal cytology: Maturation index shifts to the left from the midcycle to the mid second half of cycle due to the effect of progesterone (p. 92). Single smear on day 25 or 26 of the cycle reveals features of progesterone effect, if ovulation occurs.
Hormone estimation
■Serum progesterone: Estimation of serum proges- terone is done on day 8 and 21 of a cycle (28 days). An increase in value from less than 1 ng/mL to greater than 6 ng/mL suggests ovulation.
Serum LH: Daily estimation of serum LH at midcycle can detect the LH surge. Ovulation occurs about 34-36 hours after beginning of the LH surge. It coincides about 10-12 hours after the LH peak.
■ Serum estradiol attains the peak rise approximately 24 hours prior to LH surge and about 24-36 hours prior to ovulation. The serum LH and estradiol estimation is used for in vitro fertilization.
■Urinary LH: LH kits are available to detect midcycle LH surge. Ovulation usually occurs within 14-24 hours of detection of urine LH and almost always within 48 hours. (The test should be done on a daily basis. It is started 2-3 days before the expected surge depending upon the cycle length).
Endometrial biopsy
Endometrial tissues to detect ovulation (endometrial sampling) can easily be obtained as an outpatient procedure using instruments such as Sharman curette or Pipelle endometrial sampler.
When to do? Biopsy is to be done on 21st-23rd day of the cycle. Barrier contraceptive should be prescribed during the cycle to prevent accidental conception.
Findings: Evidences of secretory activity of the endometrial glands in the second half of the cycle give not only the diagnosis of ovulation but can predict the functional integrity of the corpus luteum.
Subnuclear vacuolation is the earliest evidence appearing 36-48 hours following ovulation.
Cause: The secretory changes are due to the action of progesterone on the estrogen primed endometrium. Endometrial biopsy is not done as a routine for detection of ovulation.
Hysteroscopy is useful to exclude intrauterine pathology (polyps, fibroid). It may be done as an OPD procedure.
Sonography
Serial transvaginal sonography (TVS) during midcycle can precisely measure the Graafian follicle just prior to ovulation (18-20 mm). It is particularly helpful for confirmation of ovu- lation following ovulation induction, artificial insemination, and in vitro fertilization. The features of recent ovulation are: Collapsed follicle and fluid in the pouch of Douglas. TVS can detect endometrial thickness. Trilaminar endome- trium with a thickness >8 mm is favorable for implantation.
Direct
Laparoscopy
Laparoscopic visualization of recent corpus luteum or detection of the ovum from the aspirated peritoneal fluid from the pouch of Douglas is the only direct evidence of ovulation.
Conclusive
Pregnancy is the surest evidence of ovulation.
Luteal Phase Defect
Diagnosis of LPD is difficult. However, it is based on the following:
■BBT chart: (a) Slow rise of temperature taking 4-5 days following the fall in the midcycle; (b) Rise of temperature sustains less than 10 days.
■Endometrial biopsy-biopsy done on 25-27th day of the period reveals the endometrium at least 3 days out of phase (Example: If the biopsy is done on 25th day of cycle, the endometrial changes observed correspond to the day 22). This lag phase endometrium must be proved in two consecutive cycles. However, it is not conclusive.
■Serum progesterone estimated on 8th day following ovulation is less than 10 ng/mL.
Luteinized Unruptured Follicle
Luteinized unruptured follicle (LUF) syndrome refers to an infertile woman with regular menses and presumptive evidences of ovulation without release of the ovum from the follicle (trapped ovum). The features of ovulation, formation of corpus luteum and its stigma are absent. It is often associated with pelvic endometriosis.
Diagnosis: In the presence of biologic effects of progesterone in the early luteal phase:
■Sonography: Persistence of echo-free dominant follicle beyond 36 hours after LH peak.
■ Laparoscopy: Failure to observe a stigma of ovulation.
■ Ovarian biopsy: Conclusive proof is determination of ovum amidst the structure of corpus luteum.
Investigations of Female Partner
b) Diagnosis of Tubal and peritoneal factors
-Tests to assess Tubal Patency(image)
Tubal Factors (Table 17.5)
The anatomical patency and functional integrity of the tubes are assessed by the following tests:
Insufflation Test (Rubin’s Test)
Principle: The underlying principle is that the cervical canal is in continuity with the peritoneal cavity through the tubes. As such, entry of air or CO2 into the peritoneal cavity when pushed transcervically under pressure, suggests of tubal patency (it is not commonly done these days).
When to be done? It should be done in the postmenstrual phase at D7 to D10 of this cycle.
Limitation: It should not be done in the presence of pelvic infection.
Observations: The patency of the tube is confirmed by: (1) Fall in the pressure when raised beyond 120 mm Hg; (2) Hissing sound heard on auscultation on either iliac fossa and (3) Shoulder pain experienced by the patient (irritation of the diaphragm by the air).
Drawbacks: In about one-third of cases, it gives false-negative findings due to cornual spasm. It also cannot identify the side and site of the block in the tube. As such, it is inferior to other methods of tubal study. This test is not commonly done these days.
Hysterosalpingography (HSG) (Fig. 17.3) (see detail p. 494)
Principle: The principle is the same like that of insufflation test. Instead of air or CO₂, dye is instilled transcervically. When to be done?: D7-D10 of the cycle.
Limitation: As in D&I.
Advantages: It has got distinct advantages over insuffla-
tion test. It can precisely detect the side and site of block in the tube. It can reveal any abnormality in the uterus (congenital or acquired like synechiae, fibroid). As such, insufflation of the tubes has largely been replaced by HSG (Fig. 17.3).
Disadvantages: It involves radiation risk amongst others.
Laparoscopy and Chromopertubation (Fig. 17.4)
Laparoscopy is the gold standard (definitive method) for evaluation of tubal factors of infertility. The indica- tions of its use are mentioned in Table 17.6.
Drawbacks: Laparoscopy is more invasive than hystero-
salpingography (HSG). It cannot detect abnormality in the
uterine cavity or tubal lumen. Thus, the two procedures (HSG and laparoscopy) should be regarded as comple- mentary to each other and not a substitute to the other procedure.
When to be done? It is commonly done in the proliferative phase.
Sonohysterosalpingography
Principle: Normal saline is pushed within the uterine cavity with a pediatric, Foley catheter. The catheter balloon is inflated at the level of the cervix to prevent fluid leak. Ultrasonography of the uterus and fallopian tubes are done. Ultrasound can follow the fluid through the tubes up to the peritoneal cavity and in the pouch of Douglas. Advantages: It is a noninvasive procedure. It can detect uterine malformations, synechiae, or polyps (superior to HSG). Tubal pathology could be detected as that of HSG. There is no radiation exposure.
Falloposcopy
It is to study the entire length of tubal lumen with the help of a fine and flexible fiberoptic device. It is performed through the uterine cavity, using a hysteroscope. It helps direct visualization of tubal ostia, mucosal pattern, intratubal polyps, or debris.
Salpingoscopy
Tubal lumen, is studied introducing a rigid endoscope Through the fimbrial end of the tube. It is performed through the operating channel of a laparoscope.
Investigations of Female Partner
c) Diagnosis of Uterine Pathology
d) Diagnosis of Cervical Pathology
Uterine factor: Uterine factors commonly associated with subfertility are submucous fibroids, congenital malformations (Ch. 4), and intrauterine adhesions (Asherman’s syndrome). They are more likely to cause recurrent pregnancy loss rather than primary infertility.
Ultrasonography, HSG, hysteroscopy, and laparoscopy are needed in the evaluation of uterine factor for subfertility.
Hysteroscopy (p. 520)
It is the gold standard for visualizing the uterine cavity and the tubal ostia. Besides diagnosis, therapeutic benefits of hysteroscopy are: (a) Polypectomy for endometrial polyp; (b) Submucous resection of myoma; (c) Hysteroscopic adhesiolysis; and (d) Resection of uterine septum.
Cervical factor (Table 17.7): The cervix functions as a biological valve. This is because in the proliferative phase, it permits the entry of sperm and in the secretory phase, hinders their penetration. As such, dysfunction at this level should be carefully evaluated.
Postcoital test (PCT) (Sims-Huhner test)
Principle: PCT is to assess the quality of cervical mucus and the ability of sperm to survive in it. PCT is rarely done these days. Sperm cervical mucus contact test (SCMCT) not done presently.
Endocrinopathy: In-depth investigations in suspected or overt endocrinopathy with or without menstrual abnormality or ovarian dysfunction include estimation of serum TSH, prolactin, FSH, LH, dehydroepiandrosterone sulfate, testosterone, and progesterone in mid luteal phase. In cases with family history of diabetes, postprandial blood sugar is to be estimated.
Immunological factor: Human sperm has immuno- logic potential. The antibodies against sperm affect fertility by immobilizing sperm or causing sperm agglutination.
Most common variety of antisperm antibodies are IgG, IgM, and IgA isotypes. IgG may be found in cervical mucus, serum, and semen. Agglutinating antibodies of IgA class are found in cervical mucus and seminal plasma. The IgM (larger) molecules are found exclusively in the serum. These immunoglobulins can bind to different parts of the sperm (e.g. head, body, or tail) and make them immobile.
Detection of antisperm antibody has not been found to be helpful in the management of infertility. Treatment of antisperm antibodies has not improved the pregnancy outcome. Such cases are treated with IUI, IVF, or ICSI.
Unexplained infertility is defined when no obvious cause for infertility has been detected following all standard investigations. These include semen analysis, ovulation detection, tubal and peritoneal factors, endocrinopathy, and PCT. Qverall incidence is 10-20%. With expectant management about 60% of couples with unexplained infertility will conceive within a period of 3 years. IVF and ET may be an option for those who fail to respond.
- Indications of Laproscopy in Infertility - Benefits of Laproscopic evaluation in Infertility
BENEFITS OF LAPAROSCOPIC EVALUATION
• Tubes: For detection of tubal patency, block (site and side), motility, hydrosalpinx change, peritubal adhesions, fimbrial agglutination.
• Ovaries: PCOS changes, endometriosis, PID, adhesions
• Uterus: Anomalies, fibroids.
• Peritoneal factors: Adhesions, PID, endometriosis, tuberculosis.
• Therapy at the same sitting (as appropriate).
