2. Management is based on the assessment of coital function, semen examination report and
the result of the post- coital and immunological tests, as well as hormonal reports.
4. STEPS TO MANAGE
1. Education: This involves: (i) sexual counselling—coital frequency and timing, (ii)
coital position and (iii) masturbation leading to sperm dilution.
2. Substance abuse: Advice on avoidance of tobacco (smoking, chewing), moderation in
consumption of alcohol and avoidance of drug abuse. Antioxidants, vitamin E improve
semen parameters. Pentoxifylline 400 mg t.i.d improves sperm motility.
3. Reduce heat around the scrotum: Avoid hot baths, wear loose cotton underwear
(cotton clothing to encourage ventilation),avoid strenuous activities and occupation in
hot environment and control obesity.
4. Correct endocrinopathies: Prompt attention to diabetes and thyroid disorders.
5. 4. Surgical:
• Surgical correction of varicocele after the diagnosis has been confirmed on
ultrasound scanning, helps to improve sperm motility. Though recently per-
cutaneous embolization of varicocele is attempted, damage to the testicular artery
and recurrence of varicocele make microsurgery the gold standard and the best
option for varicocele.
• Surgical correction of the undescended testes in childhood improves the semen
quality in 60–70% cases. The obstruction in the vas by vaso-vasal or vaso-
epididymal anastomosis will restore patency.
• Ephedrine 60 mg orally four times a day for 2 weeks or a adrenergic drug such
as phenylephrine (2.5 mg) is tried in retrograde ejaculation. If this fails
reconstruction of the bladder neck is recommended.
5. Antibiotics: Infection indicates the need for appropriate antibiotics to treat
epididymo-orchitis, prostatitis and sexually transmitted diseases. Doxycycline
100 mg bid for 6 weeks is beneficial for chlamydial infection.
6. 4. Anti-oxidants : role of oxidating stress on sperm function through pro- oxidants
liberated by leucocytes, and abnormal sperms is now realized. Some have observed
improved sperm count by prescribing lycopene 2 mg daily and vitamin E.
Antioxidants contain vitamin E 100 mg, vitamin C 500–1000 mg, N-acetylcysteine
200–500 mg t.i.d., carnitine 3 g daily, selenium 225 mg, pentoxylline 400 mg t.i.d.
Lycopene 2 mg daily for 6 months is reported to improve quality of the sperms and
prevent sperm DNA damage.
5. Premature ejaculation: Selective serotonin reuptake inhibitors take 2 weeks to
reach the therapeutic level, but dapoxetine works within 1 h; 30–60 mg is taken 1 h
before intercourse.
6. Hormones: Testosterone, pituitary hormones and GnRH have all been tried to
improve spermatogenesis with variable results. Bromocriptine is useful in
hyperprolactinaemia.
7. HORMONAL THERAPY
The use of certain medical treatment has been associated with an increase in sperm
production or motility, and primarily focuses on optimizing testosterone (T) production from
the Leydig cells, increasing follicle-stimulating hormone (FSH) levels to stimulate Sertoli
cells and spermatogenesis, and normalizing the T to estrogen ratio.
8. 1. HCG: 3000 IU IM thrice weekly for 12 weeks. Alternatively, 5000 IU twice weekly may
be given. Lately 2500 IU dose has been recommended. Thereafter, 37.5–75 mg FSH
subcutaneously is added thrice a week. Follow-up with testosterone level and semen
analysis. It takes 6–9 months to produce normal semen counts. 1. Testosterone—25–50
mg daily orally improves testicular function. A larger dose of 100–150 mg daily
suppresses spermatogenesis. After a 3 month course of treatment, re- bound phenomena
occur with improved spermatogenesis.
2. Testosterone: 25–50 mg daily orally improves testicular function. A larger dose of 100–
150 mg daily suppresses spermatogenesis. After a 3 month course of treatment, re- bound
phenomena occur with improved spermatogenesis.
9. 3. Clomiphene: 25 mg daily for 25 days followed by rest for 5 days is given cyclically for
3–6 cycles. It is recommended in hypogonadal infertility, but is not effective in
hypogonadal hypopituitarism. Instead of clomiphene, letrozole 2.5 mg may be employed.
4. Human menopausal gonadotropin (hMG): 150 IU thrice a week for 6 months is
recommended in pituitary inadequacy, but it may take as long as 1 year to induce
spermatogenesis.
5. GnRH: is indicated in hypothalamic failure.
GnRH 5–20 mcg subcutaneously 2 hourly for 1–2 years, preferably with add back therapy
with oestrogens or progesterones. Nasal spray is also available.
6. Tamoxifen:—10 mg daily for 6 months has been found effective in some cases.
10. 7. Dexamethasone: 0.5 mg daily or 50 mg prednisone daily for 10 days in each cycle for 3–6
months is recommended in the presence of spermal antibodies. About 25–40% pregnancy rate is
observed, though avascular necrosis (AVN) of the head of the femur and osteopenia as side effects
have to be borne in mind in prolonged therapy. Cyclosporin A 5–10 mg/kg daily for 6 months is
better than corticosteroids in T-cell suppression. If corticosteroids are contraindicated, an anti
inflammatory agent such as naproxen 50 mg twice daily may lower the antibody levels.
8. Sildenfil (Viagra):25–100 mg 1 h before intercourse improves erectile function but recent reports
on cardiac ischaemic heart disease is alarming, and should be prescribed with care. Colour visual
disturbances, headache, rhinitis and dyspepsia have also been reported. It is contraindicated in men
on hypotensive drugs. Sildenafil is used only in erectile function, and does not improve libido. With
25–100 mg orally 1 h before intercourse, the effect lasts for 1–2 h. The drug is effective in 50–80%
cases.
11. It is contraindicated in the following:
n
1. Retinitis pigmentosa.
2. Diabetic retinopathy.
3. Patient on antihypertensive drugs, nitrates.
4. Cardiac disease, previous myocardial infarct, stroke.
Self-injection of vasoactive drugs for erection is taken 5–10 min before intercourse and is 50–70%
effective. Side effects are penile brosis, infection and prolonged erection. Prostaglandin E1 causes
penile vasodilatation. Urethral pellets are also available. Penile vascular surgery and penile
prosthesis implantation rods are also available for erectile dysfunction.
Penile implant AMS 700 is 3-piece inflatable penile prosthesis which is now available.
12. ARTIFICIAL INSEMINATION
Artificial insemination (AI) is the deliberate introduction of sperm into a female's uterus or
cervix for the purpose of achieving a pregnancy through in vivo fertilization by means other
than sexual intercourse. An artificial insemination with husband’s semen for 4 cycles has
yielded 30% overall success with 10% success per cycle. The results are better if combined
with ovulation induction for multiple ovulation, and this is the practice recommended today. It
is indicated in the following:
• Chronic medical disorder.
• Oligospermia after sperm washout.
• Impotency ejaculatory failure.
• Premature ejaculation, retrograde ejaculation.
• Hypospadias.
• Anti-spermal antibodies in the cervical mucus.
• Unexplained infertility.
13. • It is also possible to freeze the semen if the husband is a frequent traveller and not available at
the time of ovulation for IUI.
• The semen can be frozen and used later in case the husband needs to undergo radio- therapy or
chemotherapy.
• X–Y fractionation of sperms for sex selection, in genetic and chromosomal abnormalities.
• HIV-positive male or female.
Techniques used for artificial insemination include:
1. Intrauterine (IUI) and intrafallopian done via hysteroscope or by blind procedure,
2. Intracervical,
3. Pericervical and vaginal
4. Direct intraperitoneal insemination (DIPI)
14. Intra Uterine Insemination (IUI):
Intrauterine insemination (IUI) is a fertility treatment that
involves placing sperm inside a woman’s uterus to
facilitate fertilization. The goal of IUI is to increase the
number of sperm that reach the fallopian tubes and
subsequently increase the chance of fertilization.
IUI provides the sperm an advantage by giving it a head
start, but still requires a sperm to reach and fertilize the
egg on its own. It is a less invasive and less expensive
option compared to in vitro fertilization.
Intrauterine insemination is normally done once around ovulation, some prefer to do twice in each
cycle. IUI is repeated up to 3–6 cycles. One moves to IVF or intracytoplasmic insemination if
conception fails. The IUI should be done within 90 min of collection of semen, for optimal results.
Prophylactic progesterone is recommended to the woman in the luteal phase.
15. Indications are as follows:
• Chronic ill health and disease.
• Azoospermia.
• Immunological factors not correctable.
• Genetic disease in the husband.
• Homozygous Rh positive husband with previous
pregnancy losses.
16. The donor for insemination is screened for HIV, sexually transmitted infection and
hepatitis B, and good quality of semen confirmed. The frozen semen is stored for 6
months to minimize HIV transmission. If the donor remains HIV negative by the end
of this period, the insemination is thawed and used.
17. MANAGEMENT OF AZOOSPERMIA
Azoospermia, also known as no sperm count, is a male fertility issue that occurs when there
is virtually no sperm in a man's ejaculate. Azoospermia is a frequent contributing factor
toward the inability to conceive.
Obstructive azoospermia requires vasogram to study the site and nature of blockage.
Vaso-vasal anastomosis has been successful in a few cases. The advantage of surgery over
ICSI is that it is a one time treatment and cost effective, if successful with permanent effect.
Subsequent spontaneous pregnancies are possible.
Five per cent males suffer from azoospermia. Depending upon its cause, especially in
hormonal deficiencies, GnRH and pituitary hormones have been used to induce
spermatogenesis.
18. Other methods in male infertility are:
• IVF.
• Gamete intrafallopian transfer (GIFT) technique.
• Microassisted fertilization (MAF) technique.
• Microsurgical epididymal sperm aspiration (MESA) or percutaneous epididymal sperm
aspiration (PESA).
• Testicular biopsy, sperm retrieval
• Even spermatids have been utilized in assisted reproduction.
19. IVF
In vitro fertilization (IVF) is a complex series of procedures used to treat fertility or
genetic problems and assist with the conception of a child.
During IVF, mature eggs are collected (retrieved) from ovaries and fertilized by sperm in
a lab. Then the fertilized egg (embryo) or eggs are implanted in the uterus. One cycle of
IVF takes about two weeks.
20. In this, induction of ovulation is done with clomiphene, FSH/LH or GnRH depending upon the
woman’s response to the drug. The aspiration of mature oocytes is done under ultrasonic
guidance. The oocytes are kept in the specific culture for a few hours, to complete oocyte
maturation. About 50,000 selected sperms are used for insemination.
Eighteen hours after insemination, oocytes are observed for the presence of pronuclei (sign of
fertilization) and cultured for a further 24 h. At 2- to 4-cell stage, two-embryo transfer (ET) into
the uterine cavity 1 cm below the fundus is performed. The woman is allowed to go home 2–3 h
following ET.
The indications for IVF are as follows:
1. Idiopathic or unexplained male and female infertility.
2. Immunological factor in male and female.
3. Blocked fallopian tubes or failed tubal surgery.
4. Failed intrauterine or fallopian insemination.
5. Mild endometriosis.Abnormal semen ndings.
6. Donor semen or sperm.
21. GIFT
GIFT is an assisted reproductive procedure which involves removing a woman’s eggs,
mixing them with sperm, and immediately placing them into a fallopian tube.
One of the main differences between this procedure and in vitro fertilization (IVF) and
zygote intrafallopian transfer (ZIFT) procedures is that with GIFT the fertilization process
takes place inside the fallopian tube rather than in a laboratory. However, healthy tubes are
necessary for GIFT to work.
22. It involves aspiration of oocytes following ovulation induction either laparoscopically or under
ultrasound guidance trans- vaginally. Laparoscopic route is preferred as it is anyway required
for sperm and oocyte transfer into the fallopian tube. Two hours before aspiration, the semen
is prepared, washed from the seminal plasma and left in culture medium at 37°C. The oocytes
(2 per tube) are mixed with 50,000 sperms and transferred to each ampullary portion of the
fallopian tube 4 cm from the mbrial end. The vol- ume transferred is 10–20 μ (micron).
GIFT technique allows in vivo fertilization in the natural site (fallopian tube) unlike IVF, but
needs laparoscopy technique (invasive).
Lately, transfer of oocytes and sperms is attempted by transuterine catheterization of the tube
(falloscopically) and laparoscopy is avoided.
PROCEDURE:
23. The indications for GIFT are:
1. Unexplained infertility.
2. Failed intrauterine insemination (IUI).
3. Male infertility.Immunological factor in male.
4. Immunological factors in the cervix.
5. Donor semen required (rare).
Both the fallopian tubes must be patent. The results are better with GIFT than IVF, i.e. 45% success
versus 15–20%, but success rate with IVF is improving; besides laparoscopy is not required.
Abortion rate of 10–15%, ectopic preg- nancy (7%) and multiple pregnancy (20–50%) have been
reported with GIFT.
Disadvantage—fertilization cannot be con rmed.
24. ICSI - Intra Cytoplasmic Sperm Injection
ICSI is indicated and proved successful in case of immotile
sperms and sperm count less than 5 million/mL with a
pregnancy rate of 30–40%. A single sperm is injected into the
cytoplasm of the oocyte, which is then incubated overnight.
Indications for ICSI are as follows:
• Sperm count less than 5 million/mL.
• Absent or reduced sperm motility.
• Abnormal sperm morphology.
• Previous IVF has failed.
• Unexplained infertility.
• Failure to penetrate zona by sperm as seen in IVF.
25. PSYCHOLOGICAL CONSIDERATION
The discovery of infertility or sterility can create shock, fear and depression in the couple.
Some feel inadequacy and shame of not being able to reproduce. Some lose their self-esteem
and feel the social disadvantage. To add to this, the strain of investigations and treatment
increase the burden not affordable to all. Sympathetic and respectful attitude by the medical
personnel will help in dealing with the infertile couple during their consultation.
Impotence caused by fatigue, drugs, multiple sclerosis and diabetes needs correction.
Similarly premature ejaculation needs physiotherapy and psychological counselling.
26. THINK!A study by an international children's charity has found
that 4 per cent of India's child population of 20 million are
orphans.
The cost per IVF cycle ranges between 1.5 to 2 lakhs. The
percentage of success rate even after three rounds of IVF
cycle is only 40%. And the success rate goes down with
every successive round of IVF.
So, we as doctors should encourage couples to undertake
adoption. Explain them about the importance of adoption
in India should try to make them understand Parenthood
requires LOVE and not DNA.
Its better to adopt a child who is in the need than to
struggle and create ones own breed.