INFERTILITY/SUBFERTILITY

Infertility primarily refers to the biological inability of a person to contribute to conception.

Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term.
There are many biological causes of infertility, including some that medical intervention can
treat.
World health organization
The WHO defines infertility as follows:

Infertility is the inability to conceive a child. A couple may be considered infertile if, after
two years of regular sexual intercourse, without contraception, the woman has not become
pregnant (and there is no other reason, such as breastfeeding or postpartum amenorrhoea).

Types of infertility
1.

Primary infertility: It is infertility in a couple who have never been able to conceive

despite regular (2-3 times per week) unprotected intercourse for at least one year.
2. Secondary infertility: It is failure to conceiving after already having conceived (and
either carried the pregnancy to term or had a miscarriage) despite 12 months of
unprotected intercourse.

Subfertility: The couple had difficult in conceiving jointly because both partners may
have reduced fertility. A less than normal capacity for reproduction.

Unexplained Infertility
A couple that has failed to establish a pregnancy despite an evaluation uncovering no
obvious reasons for infertility is said to have unexplained infertility.Unexplained infertility
should only be diagnosed when ovulation has been established, tubes are patent, adeuqate
sperm-cervical interaction has been show, with no endometriosis, adnexal adhesions or
intrauterine pathology and male partner has demonstrated normal sperm productio.

Fecundability
It is defined as the probability of achieving a pregnancy within one menstrual cycle. In a
healthy young couple it is 20% fecundability is the probability of achieving a live birth
within a single cycle.
Prevalence
Prevalence of infertility varies depending on the definition, i.e. on the time span involved in the
failure to conceive.
Some estimates suggest that worldwide "between 3 and 7% of all couples or women have an
unresolved problem of infertility. Many more couples, however, experience involuntary
childlessness for at least one year: estimates range from 12% to 28%."
Women become less fertile as they get older. For woman aged 35 about 94 out of every 100 who
have regular unprotected sexual intercourse will get pregnant after 3 years of trying. For woman
aged 38 however only 77 out of every 100 will do so. The effect of age upon mens fertility is
less clear.
Requirement for fertility
Male

Testes
Patent ductal system (at least one side)
Ability to maintain erection
Ability to achieve ejaculation
Healthy spermatozoa

Female

At least one ovary

At least one well functioning fallopian tube
Well developed and mature uterus
Capable external genitalia
Adequate sex hormone

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 through investigations with modern technical
facilities. It is also strange that 4 to 10 patients of unexplained category
become pregnant within 3 years without having any specific treatment.

Data from UK, 2009

Common causes of infertility of females:

1.
2.
3.
4.
5.
6.
7.
8.

Pelvic inflammatory disease

Advanced maternal age
Tobacco smoking
Body weight and eating disorders
Chemotherapy
Diabetes mellitus
Radiatiotherapy
Genetic factors
Chromosomal abnormalities

9. Hypothalamic-pituitary factors

Hypothalamic dysfunction

Hyperprolactinemia

Hypopituitarism

10. Ovarian factors

Diminished ovarian reserve, also see Poor Ovarian Reserve

Premature menopause

Anovulation

Ovarian cancer

Luteal dysfunction

11. Tubal (ectopic)/peritoneal factors

Tubal blockage

Previous tubal ligation

12. Uterine factors

Uterine malformations

Uterine fibroids (leiomyoma)

Endometriosis

13. Cervical factors

Cervical stenosis

Antisperm antibodies

Non-receptive cervical mucus

14. Vaginal factors

Vaginismus (psychosocial problem)

Vaginal obstruction

Causes of infertility in male

1. Pre-testicular causes
Pre-testicular factors refer to conditions that impede adequate support of the testes and include
situations of poor hormonal support and poor general health including:

Hypogonadotropic hypogonadism due to various causes

Obesity increases the risk of hypogonadotropic hypogonadism.

Drugs, alcohol

Strenuous riding (bicycle riding, horseback riding)

Medications, including those that affect spermatogenesis such as chemotherapy, anabolic

steroids, cimetidine, spironolactone; those that decrease FSH levels such as phenytoin; those
that decrease sperm motility such as sulfasalazine and nitrofurantoin

2. Tobacco smoking
Male smokers also have approximately 30% higher odds of infertility. There is increasing
evidence that the harmful products of tobacco smoking kill sperm cells.
3. Testicular factors
Testicular factors refer to conditions where the testes produce semen of low quantity and/or poor
quality despite adequate hormonal support and include:

Age

Genetic defects on the Y chromosome

Abnormal set of chromosomes

Neoplasm, e.g. seminoma

Cryptorchidism

Varicocele (14% in one study)

Trauma

Hydrocele

Mumps

Malaria

Testicular cancer

Idiopathic oligospermia - unexplained sperm deficiencies account for 30% of male

infertility.

Radiation therapy

4. Post-testicular causes
Post-testicular factors decrease male fertility due to conditions that affect the male genital system
after testicular sperm production and include defects of the genital tract as well as problems
inejaculation:

Vas deferens obstruction

Infection, e.g. prostatitis

Ejaculatory duct obstruction

Hypospadias

Impotence

low sperm count

Immotile sperm

Diagnosis
Diagnosis of infertility begins with a medical history, occupational history, sexual
history and full physical examination. The healthcare provider may order tests, including the
following:

Laboratory Investigations
1. Hormone testing, to measure levels of female hormones at certain times during
a menstrual cycle, day 2 or 3 measure of FSH and estrogen, to assess ovarian reserve
2. Measurements of thyroid function (a thyroid stimulating hormone (TSH) level of
between 1 and 2 is considered optimal for conception)
3. Measurement of progesterone in the second half of the cycle to help confirm ovulation
4. Serum LH, testosterone and prolactine
5. Semen analysis
The volume of the semen sample, approximate number of total sperm cells, sperm
motility/forward progression, and % of sperm with normal morphology are measured.
Normal semen values as suggested by WHO (2002):

Volume: 2.0 ml or more

PH: 7.2 7.8
Sperm concentration: 20 million/ml or more
Total sperm count: >40 million per ejaculate
Motility: 50% or more normal form
Morphology: 15% or more

Viability: 75% or more living

Leucocytes: less than 1 million/ml

Semen deficiencies are often labeled as follows:

Oligospermia or Oligozoospermia - decreased number of spermatozoa in semen

Aspermia - complete lack of semen

Hypospermia - reduced seminal volume

Azoospermia - absence of sperm cells in semen

Teratospermia - increase in sperm with abnormal morphology

Asthenozoospermia - reduced sperm motility

6. Blood sample
Common hormonal test include determination of FSH and testosterone levels.
7. Urine routine examination

Examination and imaging

An endometrial biopsy, to verify ovulation and inspect the lining of the uterus

Laparoscopy, which allows the provider to inspect the pelvic organs

Fertiloscopy, a relatively new surgical technique used for early diagnosis (and
immediate treatment)

Pap smear, to check for signs of infection

Pelvic exam, to look for abnormalities or infection

A postcoital test, which is done soon after intercourse to check for problems with
sperm surviving in cervical mucous (not commonly used now because of test
unreliability)

Basal body temperature

Cervical muscus examinatio

Special X-ray tests

Fructose content in the seminal fluid

Vasogram

Transrectal USG

Testicular biopsy

There are genetic testing techniques under development to detect any mutation in genes
associated with female infertility.

Management of sub-fertility
1.
2.
3.
4.

Assurance: The couple should be handling tactfully to minimize psycholigical upset.

Management of body weight.
Cessation of smoking and alcohol.
Evaluation of coital problems.

General care:

Improvement of general health

Reduction of weight in obese.
Avoidance of alcohol and heavy somking.
Avoidance of tight and warm undergarments or occupation that may elevate testicular

temperature.
Use of vitamins E, C, D, B12 and folic acid.
Medication that interfere spermatogenesis should be avoided.

Medical treatments
Medical treatment of infertility generally involves the use of fertility medication, medical device,
surgery, or a combination of the following. If the sperm are of good quality and the mechanics of
the woman's reproductive structures are good (patent fallopian tubes, no adhesions or scarring),
physicians may start by prescribing a course of ovarian stimulating medication. The physician
may also suggest using a conception cap cervical cap, which the patient uses at home by placing
the sperm inside the cap and putting the conception device on the cervix, or intrauterine

insemination (IUI), in which the doctor introduces sperm into the uterus during ovulation, via a
catheter. In these methods, fertilization occurs inside the body.
If conservative medical treatments fail to achieve a full term pregnancy, the physician may
suggest for assisted reproductive (ART) techniques.

Assisted Reproductive Technology (ART) Techniques

1. In-vitro fertilization IVF
In vitro fertilization describes the laboratory technique where fertilization occurs outside the
body and is one of the main types of ART. It is indicated in cases where the female partner has
uterine tube occlusion, endometriosis or cervical mucus problems or where male factors are the
main problem. It may be appropriate for cases of unexplained infertility.
Under this technique, the fallopian tubes are by-passed and many eggs produced with exogenous
gonadotrophins to induce multiple follicular developments (aspirated under ultrasound control).
An injection of HCG is given 34-38 hours before egg collection. The eggs are then fertilized
using selected sperms in the laboratory. A few days later, two of the embryos thus produced are
transferred into the uterus for woman <40 and 3 embryos for women aged >40 and the surplus
embryos stored for future use.
Factors affecting treatment outcome include:
Advancing age of woman
Prolonged infertility
The presence of subtle male factors
High basal levels of follicle stimulating hormone and high bodymass index in the woman
2. Intra-cytoplasmic sperm injection- ICSI

Developed in 1992, this is a sophisticated technique where a single sperm is injected directly into
the cytoplasm of an egg with a fine glass needle to facilitate fertilization. It is useful if the
sperms are extremely poor in number and function. Fertilization rates of 70% have been
achieved with ICSI.
3. Sperm-egg-embryo donation
Where the couple has no sperms, donated sperm could be used for IUI or IVF. If the wife has no
eggs, donated eggs or embryos could be used for IVF.

4. Surrogacy
If the wife has no uterus or pregnancy is contraindicated for medical reasons, another woman
could nurture the pregnancy. The embryo (sperm from husband with egg from surrogate; both
sperm and egg from donors or embryo from donor) could be used for surrogacy.
5. Intrauterine Insemination
IUI involves the introduction of prepared sperm into the uterine cavity around the time of
ovulation (spontaneous or induced). This technique is used for couples with:

Low semen volume.

Poor sperm parameters.

Defects of sperm-cervical mucus interaction.

Unexplained infertility.

Donor insemination is also used to treat couples where the male partner is azoospermic. The
probability of a successful conception with IUI is greater in the first 4 attempts with the
likelihood of success being reduced thereafter.
6. Gamete Intrafallopian Transfer (GIFT)
GIFT involves recovery of oocytes (in stimulated or natural cycles) from the ovaries. They are
then mixed with spermatozoa and transferred into one or both Fallopian tubes. This technique is
usually used for couples with:

Anovulatory infertility.

Endometriosis.

Unexplained infertility.

Defects of sperm-cervical mucus interaction.

Female immunologic infertility.

Multifactorial infertility.

7. Zygote Intra-fallopian Transfer (ZIFT)

Zygote intra-fallopian transfer was first described by Devorly et al in 1986. In this technique, the
zygote (following one of in vitro-fertilization) is place in the fallopian tube by either through the
abdominal ostion by laparoscope or through the uterine ostion under ultrasonic guidance. This is
suitable alternative of GIFT when defect lies in the male partner or in case of failed GIFT. GIFT
and ZIFT should be avoided when tubal factors for infertility are present.
Ovulation disorder treatment
1. Clomifene citrate (CC) - an anti-oestrogen, is the best initial treatment for the majority of
women with anovulatory problems.Tamoxifen is an alternative. Treatment should be limited
to the minimum effective dose (50-100 mg for first five days of the cycle) and to no more
than six ovulatory cycles. Metformin may be added in if the woman does not respond to
clomifene and has polycystic ovarian syndrome (PCOS) and a BMI greater than 25 kg/m2.
Failure to conceive after successful CC-induced ovulation is indication for further
evaluation to exclude other contributing causes of infertility. The principal side-effect of CC
is multiple pregnancy, which occurs in <10%. Women who fail to ovulate with antioestrogens can be offered treatment with gonadotrophins.
2. Gonadotrophin-releasing hormone (GnRH) analogues - GnRH agonists - are most often
used in conjunction with gonadotrophins to achieve pituitary down-regulation and facilitate
cycle control in ovarian stimulation during IVF treatment. Dopamine agonists can be
considered for women with ovulatory disorders secondary to hyperprolactinaemia.
3. Surgical therapy with laparoscopic ovarian 'drilling' (LOD)
The procedure can be done on an outpatient basis with less trauma and fewer postoperative
adhesions than with traditional surgical approaches, eg wedge resection. There was a reduction
in multiple pregnancy rates for women having LOD. However, there are concerns about longterm

effects

of

LOD

on

ovarian

function.

4. Other surgical options include tubal surgery. This may be effective in women with mild
tubal disease. Tubal catheterisation or cannulation improves the chance of pregnancy in women
with proximal tubal obstruction.

Complications
There is evidence of increased rates of obstetric complications in women who require assisted
reproduction. The most important complication is ovarian hyperstimulation syndrome which
may occur when ovarian stimulation techniques are used. It usually presents with lower
abdominal discomfort, nausea, vomiting, diarrhoea and abdominal distension - signs of severe
disease, indicating a need for hospital management, include:

Presence of ascites.

Rapid weight gain.

Tachycardia.

Hypotension.

Oliguria.

Other metabolic abnormalities.

Prevention
Some cases of female infertility may be prevented through identified interventions:

Maintaining a healthy lifestyle. Excessive exercise, consumption of caffeine and alcohol,

and smoking are all associated with decreased fertility.

Treating or preventing existing diseases. Identifying and controlling chronic diseases

such as diabetes and hypothyroidism and sexually transmitted diseases .

Not delaying parenthood. Fertility does not ultimately cease before menopause, but it
starts declining after age 27 and drops at a somewhat greater rate after age 35.

Avoiding smoking as it damages sperm DNA

Avoiding heavy marijuana and alcohol use.

Avoiding excessive heat to the testes.

Sperm counts can be depressed by daily coital activity and sperm motility may be
depressed by coital activity that takes place too infrequently (abstinence 1014 days or
more).

When participating in contact sports, wear a Protective Cup and Jockstrap to protect the
testicles.

Sports

such

as

Baseball,

Football,

Cricket,

Lacrosse,

Hockey,

Softball, Paintball, Rodeo,Motorcross, Wrestling, Soccer, Karate or other Martial Arts or any
sport where a ball, foot, arm, knee or bat can come into contact with the groin.