What are the causes of Secondary Infertility?

Infertility is defined as the inability to conceive after one year of unprotected inter course. The term sub fertility is often used interchangeably with infertility. Around 85 % of the couple will conceive in first year of marriage more so in first six months, and in the next one year 7 to 8 % more will conceive. The incidence of infertility is 10 to 15 %, though the incidence of infertility is not rising but due to extensive evaluation and treatment it looks like the incidence has risen.

There has been change in evaluation and treatment of infertility. Due to advent of IVF and ART we are able to detect fertilization defect and improve the prognosis for infertile couple. Nowadays more females are opting for late pregnancies which has led to conception in older age when they are less fertile leading to increase incidence of infertility in them.

The counselling and evaluation of the infertile couple should occur with both partners together rather than with one partner being present at the initial visit. the goal for evaluating an infertile couple should be:

1. To evaluate the cause of infertility when possible and to achieve the pregnancy with the possible available treatment.

2. To provide emotional and psychological support to the couple.

3. To provide accurate information about the cause and guide them for further treatment like IVF, donor gamete and adoption.

4. To identify males having genetic defect that can be transmitted to the offspring through ART.

What are the types of infertility?

There are two types of infertility according to W.H.O:

1. Primary Infertility: When a woman is unable to ever bear a child, either due to the inability to become pregnant or the inability to carry a pregnancy to a live birth.

2. Secondary Infertility: When a women who is unable to bear a child either due to inability to become pregnant or inability to carry a pregnancy to live birth following a previous conception.

What are the causes of infertility?

If we see the process of fertilization, in the female the egg is formed, follicle ruptures and releases egg, this egg will go to fallopian tube and is able to be fertilized by the sperm for next 24 hours. In the males the sperm is formed in the testes and during intercourse the semen is deposited in the vagina, from here the sperm travels through the uterus and reaches the fallopian tube where the sperm fertilizes the ovum. The sperm is able to fertilize the ova for 3 to 5 days. So, the causes are also divided into male factor, female factor, combined and unexplained.

The causes for primary and secondary infertility as almost same with few exceptions like vasectomy in males and tubal sterilization in females.

The causes of infertility in the couple is divided according:
1. Female factor: 30-35 %
2. Male factor: 35 %
3. Combined (male and female): 20 %
4. Unexplained: 10%
A. Female factor:
 Tubal and Pelvic: 40 %.
 Ovulatory Dysfunction: 40 %.
 Unusual causes: (10%)
cervical
uterine
 Unexplained: 10 %

Tubal and Pelvic pathology:

The tubes play an important part in the process of fertilization, the egg is fertilized in the tube and it stays in the tube for next 3 to 4 days. So, the tubes are not only the site of fertilization but it nurtures the early embryo till it reaches the uterine cavity.

A history of PID, septic abortion, ectopic pregnancy, endometriosis and any tubal surgery indicates that there is some tubal pathology. It could be either a proximal tubal disease or distal tubal disease. The initial evaluation is done by a HSG followed by laparoscopy if required (abnormality seen in HSG).
Also, presence of peritoneal disease, pelvic adhesions, endometriosis, hydrosalpinx and tubal sterilization can lead to infertility in a couple who has already conceived once.

Ovulatory Dysfunction:

Decline in fertility (decreased ovarian reserve) occurs as the age of female advances. The chances of normal conception decreases from 35 years and there is a sharp fall after 40 years, only one pregnancy has been documented worldwide at the age of 44 years. The egg count as well as egg number (ovarian reserve) falls as the age of female advances this is especially important for females who marry late and plan pregnancy even later in their reproductive life. This is one of the most important cause of secondary infertility.
Drugs like alkylating agents used in chemotherapy, radiotherapy can leads to accelerated follicle depletion and decreased ovarian reserve.

ovulatory dysfunction (PCOS) accounts for 15 % of problems in infertile couple and 40 % of all female factor infertility. Menstrual history is the sufficient to form the diagnosis especially if the female has oligomenorrhea or amenorrhea.

Cervical:

Cervical mucus captures the sperm and act as a reservoir for sperm. Though cervical factor of infertility is not routinely checked since postcoital test which is used for the diagnosis of infertility in no longer recommended. Damage to cervix due to trauma, cervical conization, fibroid leads to adverse pregnancy outcomes rather than infertility.

Uterine factor:

It is a relatively uncommon cause of infertility. There could be anatomical uterine abnormalities like congenital malformations, endometrial polyp, fibroid and intrauterine adhesions.
Though these abnormalities of uterus can cause infertility. But, they adversely affect pregnancy outcome in females (like pregnancy loss, obstetric complications).

Fibroids present in 5 to 10 % of infertile women they can cause infertility especially submucous which reduces IVF success rate by 70 % and intramural by 20 to 40 %.
Endometrial polyp: A polyp greater than 1.5 cm adversely affect the conception rate so polypectomy is indicated to improve reproductive outcomes.

Chronic endometritis: It has been found that in cases of unexplained infertility or unexplained recurrent implantation failure chronic endometritis is diagnosed in 2.8 % of the patients.
Congenital uterine anomalies present in 2 to 4 % of infertile population. the prevalence is higher in females of recurrent miscarriages (13 %). In patients with history of infertility and recurrent miscarriages the incidence is 23.5 %.

Intrauterine adhesions: Most commonly (90%) occur due to curettage for pregnancy complications like missed or incomplete abortions. Adhesion formation affects endometrial receptivity leading to pregnancy failure.

Hysteroscopy is a method of choice for treatment and diagnosis of intrauterine adhesions.
Hypothalamic Pituitary Causes: Most common acquired cause being pituitary tumors, prolactinoma, females engaging in high intensity workout, drugs (psychiatric medication, antiepileptic medication).
Causes specific to secondary infertility are complications related to pregnancy: Sheehan’s syndrome, hysterectomy, postpartum curettage leading to damage to endometrium and formation of adhesions.

B. male factor:
The list of causes of male factor is long and exhaustive. much of male factor infertility is idiopathic. The list of known factors is divided into four major categories:
 Hypothalamic-pituitary disorder (1 to 2%)
 Primary gonadal disorder (30 to 40 %)
 Disorder of sperm transport (10 to 20 %)
 Idiopathic (40 to 50 %)

1. Hypothalamic Pituitary Disorders:
It contains both congenital and acquired causes.
Congenital – Kallmann syndrome.
Acquired – Pituitary tumor, Hyperprolactinemia, use of anabolic steroids (athletes, gym users), head trauma, chronic illness like diabetes, infections like meningitis and obesity.
Hypothalamic Pituitary disorders are one of the cause of male factor infertility which can be treated medically.

2. Primary gonadal disorders (defect at the level of testes):
Most common congenital cause being Klinefelter’s syndrome, y chromosome microdeletions, single gene polymorphism.
Among the acquired cause varicoceles is an important cause especially grade 3 varicocele which impairs sperm parameters.

Drugs used in treatment of cancers, radiotherapy (doses as low as 15 rads can effect spermatogenesis).
Infections like tuberculosis, leprosy, mumps can also cause gonadal dysfunction
chronic illness like cancers, chronic renal disease, cirrhosis can also cause secondary infertility.
environmental gonadal toxins like (excessive heat, smoking, pesticides) also effect testicular function leading to infertility.
3. Sperm Transport Defects:
The factors which hinders the transport of the sperm from testes to ejaculation comes under these defects. These defects could be at the level of epididymis, ejaculatory ducts and ejaculatory failure.
These defects can be both congenital and acquired. congenital causes like CBAVD, Kartagener’s syndrome, young syndrome causes primary infertility.
Acquired defects like vasectomy, ejaculatory dysfunction (spinal cord disease), infection like tuberculosis (causing epididymal obstruction), Gonorrohoea and Chlamydia also causes sperm transport defects.

 Unexplained Infertility:

Present in around 10 % to as high as 30 % in infertile couple the diagnosis of unexplained infertility is made when the semen analysis is normal, ovulatory functions is normal, uterine cavity is normal and at least one tube is patent. There is occult causes of infertility like abnormality in sperm, ovum or fertilization for which there is no valid test. Unexplained infertility could be because of fertilization failure, decreased endometrial receptivity, implantation failure, zona pellucida receptor defects.

The untreated patients of unexplained infertility have a lower cycle fecundability that is 2 to 4 % whereas, a normal fertile couple has a cycle fecundability of 20 to 25 %. After 5 years the likelihood of pregnancy is reduced to 20 %, as what it was when the efforts of conception has started.

So, what causes secondary infertility is a difficult question to answer. The causes as well as the treatment options are much similar in both primary and secondary infertility. As infertility has become more socially acceptable and couples are becoming more comfortable in seeking evaluation and treatment, we are encountering more cases of secondary infertility. So, the first step is to find the cause and then treat accordingly but most important is that the couple should not delay seeking treatment.