‘The simple union of man and wife
in love creates a brand new life.
A child to cherish, plays with, and be
their link with immortality.
What bliss and joy they anticipate.
Unless infertility becomes their fate
and buries dreams that die within
as they mourn their child who might have been.’
—Michelle Siebel md
[J Assisted reproduction Genetics. 1997;4(14)]
Procreation as a life process has been subject of study by all the human societies, though in earlier days only through art and religion. True scientific understanding and subsequent manipulation started very recently. Life process of procreation is a very complicated process and any minor deviation results into infertility. Infertility is neither strictly a physically debilitating disease nor a syndrome complex, which can be defined with set of symptoms and signs; thus, there is no specific option of treatment. However, the desire to have a child is among the strongest that people experience, and no wonder that infertility is ranked among life's greatest stress, similar in intensity to having a life threatening illness, and it also affects the psychological harmony of sexual life and social function, even in those countries where the family planning and birth control is their special policy and social vogue. Unfortunately, because infertility involves the loss of something that has never been, it goes unnoticed. Perhaps, that is why infertile couples have been called the most neglected silent minority.
The WHO has defined involuntary childlessness as a disease, and it is a fundamental human right to obtain therapy for a disease as well as relief from a non-reversible state of an anatomical or psychological variation. Therefore, they have a right to be treated by all available means of reproductive medicine.2
According to data provided by the United Nation population division in 2002, showed the world population in 2001 was 6.8 billion and half of the world's residents are women. About 20% of females are in the reproductive age and the mean incidence of infertility throughout the world is 18.7%. The number of infertility throughout the globe should be approximately about 100 million. Approximately 1 in 6 couple will experience involuntary infertility at some stage of their reproductive life
DEFINITIONS
Infertility is usually defined as the inability to conceive after one year of regular unprotected coitus, and this definition is based on a monthly conception rate of 20 – 25% in normal couples actively attempting pregnancy. Infertility is said to be primary when that couple has not previously initiated a pregnancy, and secondary when they have been successful on at least one previous occasion.
Normal, fertility can be defined as those couples who achieve a pregnancy within two years by regular coital exposure. Those couples who do not achieve a pregnancy within two years include sterile members of the population, for whom there is no possibility of natural pregnancy, and the remcunder are subfertile. Together, these comprise the infertile population. The term sterile may refer to either the male or female, whereas the term subfertile refers to the couple.
Unexplained infertility is a term applied to a subfertile couple whose standard investigations yield normal results.
Fecundability is the probability of achieving a pregnancy within one menstrual cycle. Fecundity is the ability to achieve a live birth after being exposed to the risk of pregnancy for one menstrual cycle.
Factors Responsible for Fertility
- Healthy sperm should be deposited high in the vagina.
- The sperm remains healthy and penetrate the cervical mucus to pass into the uterine cavity and thence into the uterine tubes.
- Fertilization occurs in the ampullary isthmic junction of the fallopian tube where the oocyte meets the spermatozoa.
- The fertilized oocyte migrates into the uterus when nidation and subsequent development occurs in endometrium.
Principal Causes of Impaired Fertility or Infertility
Fertilization of an oocyte by a competent sperm is a basic requirement for normal fertility. In general, normal motile spermatozoa must be able to reach the Fallopian tube and a fertilized oocyte must be capable of normal transportation within the female reproductive tract, followed by implantation at proper site in the endometrium. So, any disorders of this normal tract will give rise to infertility. Principally, the causes of infertility can be broadly defined as:3
- Male factor—may be the primary or most important in approximately 40% of couples.
- Female factor—about further 40%.
- Combination of factors or no clearly identifiable cause will characterize the remaining 20%.
Common Causes of Female Infertilty
In the WHO task force study, 22 final diagnoses were established in 7,570 women who may be broadly grouped into following:
1. Ovulatory disorders | 23.8% |
2. Tubal disease | 31.5% |
3. Endometriosis | 4.5% |
4. Idiopathic | 27.2% |
5. Other causes: | 13.5% |
- Hyper prolactinemia
- Pelvic adhesions
- Premature luteinization.
Common Causes of Male Infertility
- Defective spermatogenesis
- Undescended testis
- Varicocele, or big hydrocele
- Mumps orchitis
- Thyroid dysfunction
- Diabetes mellitus
- Obstruction of efferent duct
- Tuberculosis
- Gonococcal infections and subsequent strictures
- Post-herniorrhaphy
- Congenital atresia of vas deferens or absence of seminal vesicles
- Failure to deposit sperm high in vagina
- Impotency
- Premature or absence of ejaculation
- Hypospadias
- Error in seminal fluid
- Low fructose content
- High prostaglandin content
- Undue viscosity.
Diagnostic Procedure (According to ESHRE)
Before undertaking management of infertility it is necessary to diagnose and pinpoint the cause of infertility. Various diagnostic tests can be performed 4in the couple to find the cause. Diagnostic tests for infertility can be broadly divided into 3 categories with a view that abnormal test results will give a clue to the cause of infertility only if follow-up observation reveal a relationship with pregnancy rates.
- Some of the test results have an established association with pregnancy, e.g. semen analysis, tubal patency by hysterosalpingography or laparoscopy, and laboratory assessment of ovulation. In case, when the test results show abnormalities, such as azoospermia, bilateral tubal occlusion, anovulation, fertility is impaired, and without therapy, there are little chances of reversal.
- Some of the test results are not consistently associated with pregnancy. These are the zona-free hamster egg penetration test, postcoital test, cervical mucus penetration test, and antisperm antibody assay. These diagnostic tests may give abnormal results but may be frequently associated with subsequent fertility without therapy.
- Some of the test results may not be associated with pregnancy, such as endometrial dating, varicocele assessment, and Chlamydia testing. For these diagnostic tests, there is no existing data to confirm their association with pregnancy.
The level and degree of investigations will of course, be dependent on the sophistication of the laboratories and involve the skill of the gynecologists.
Most important starting key point is the history of the patient and the physical examination of the couple. Following this, a set of basic investigations are required. These include semen analysis, hormonal tests like E2 (estradiol), FSH (follicle stimulating hormone), LH (lutnizing hormone), and testosterone between day3 to day 5 of the female menstrual cycle. On day 21/22 of a 28-day cycle, serum progesterone and prolactin are estimated.
A diagnostic laparoscopy is also carried out as a first line of investigation based on the view that it will expedite management and give the patients where there is a history of extensive surgery or severe pelvic adhesions.
For the male partner, if the repeat semen analysis gives abnormal findings then four basic hormones are tested. These are FSH (follicle stimulating hormone), LH (Lutieinizing hormone), testosterone, and prolactin. Special sperm motility assays may be carried out. Severe oligozoospermia or azoospermia cases need karyotyping.
About 80–90% of the infertility cases are diagnosed by those above tests. Further investigations are performed for those patients with cervical mucus factor and immunological infertility.
Treatment Approach of Infertile Patient
On the basis of basic investigations treatment modality is selected. Usually the patient goes to monitoring of ovulation (MO) or induction of ovulation (IO), with timed intercourse. If these fail, then next line of treatment is an insemination program in combination with induction of ovulation. If that treatment fails, 5then an assisted reproductive technique (ART) program is initiated. There is, however, no hard and fast rule or clean cutoff criteria for the selection of the appropriate treatment modality. It depends mainly on the skill and sound knowledge of the gynecologist.
Flowchart 1.1 can at least give an idea about how the infertile patients are treated.
Success of Infertility Treatment
When talking of success rates for any type of infertility treatment, one should bear in mind that the average chance to conceive for a normally fertile couple having regular unprotected intercourse is around 25% during each menstrual cycle. It is estimated that 10% of normally fertile couple fail to conceive within their first year of attempt and 5% after two years.
Compared to normal fertility rates, couples following treatments can be expected to have an average, up to a 25% success rate per cycle of treatment. Hence, any treatment modality, need to be repeated several times before a pregnancy is achieved. Simple ovulation induction to compensate for hormonal imbalances has a success rate of more than 80% in women suffering from such disorders likely to conceive after several cycles of treatment with drugs, such as clomiphene citrate, gonadotropins, etc.