1. Introduction

This is the failure to conceive after one year of sexual intercourse without contraception.

It is described as Primary Infertility when a woman has never conceived and Secondary infertility when a woman has conceived previously.

Causes of Infertility in Women

  • Factors that affect ovulation include polycystic ovary syndrome, hyperthyroidism, hypothyroidism and premature ovarian failure (when ovaries stop working before the age of 40).
  • Endocrine disorder in a woman
  • Bilateral occlusion of fallopian tubes as a result of diseases such as pelvic inflammatory disease (PID), and scarring from cervical or pelvic surgery, among others.
  • Previous infections with TB, schistosomiasis, and filariasis among others.
  • Abnormalities of cervical mucus
  • Submucosal fibroids
  • Endometriosis (especially when endometrium has grown on/in ovaries)
  • Sperm antibodies
  • Drugs such as NSAIDs, spironolactone, anti-cancers and neuroleptics
  • Congenital disorders
  • Age
  • Idiopathic (in about 25% of cases)
  • Being underweight/overweight
  • Smoking
  • Stress

Causes of Infertility in Men

  • Blocking of sperm ducts in males due to infections such as STIs
  • Azoospermia (no sperm at all)
  • Asthenozoospermia (low sperm motility)
  • Oligospermia (low sperm count)
  • Teratozoospermia (abnormal sperm morphology)
  • Hypogonadism
  • Retrograde ejaculation
  • Defects/conditions of testicles such as testicular injury, cancer, infection and failure to descend
  • Stress
  • Smoking
  • Being underweight or overweight
  • Drug abuse (such as anabolic steroids)

2. Symptoms and Signs

Failure to conceive after one year of sexual intercourse without contraception.

3. Diagnosis

  • Clinical evaluation of couples
  • Analysis of semen
  • Basal body temperature
  • Dye laparoscopy
  • Endometrial biopsy
  • Hormone analysis
  • Hysterosalpingography (HSG) for tubal patency (dye or saline and air is injected in the cervix and patency of the fallopian tube is observed by ultrasound)

4. Differential diagnosis

  • UTIs
  • Various cancers
  • Infertility of a partner

5. Management

Fertility treatments in women is divided into three categories namely medication treatments, surgical treatments and assisted Reproductive Technology (ART).

a. Medication Treatment of Infertility

Drugs are mainly useful in the treatment of problems in ovulation due to hormonal imbalance without any other challenge.

i. Clomiphene

It is used in the treatment of infertility due to anovulation or oligo-ovulation.

The following conditions must be met for the drug to be effective as an anti-infertility agent: adequate sperm by the sexual partner, functional hypothalamic-hypophyseal-ovarian systems and adequate endogenous estrogen.

It is an anti-oestrogen that exerts its effects by competing with estrogen for binding sites at the hypothalamic level. In effect, FSH and LH secretions are increased.

Dose:

50mg OD x 5/7 starting from the 3rd to 5th day of menstruation or any day if the cycle has ceased. If ovulation does not occur after the 1st course a second course is given: 100mg OD x 5/7.

ii) FSH

It is mainly used after the failure of clomiphene therapy.

A stepwise gradually increasing dosing scheme can be used. Starting dose of 75 IU is given for up to 14 days. The dose is then increased by 37.5 IU at weekly intervals until follicular growth and/or serum oestradiol levels indicate an adequate response (max. dose 300 IU).

The patient is treated until ultrasonic visualizations and/or serum estradiol determinations indicate pre-ovulatory conditions equivalent to or greater than those of the normal individual followed by hCG, 5000 IU to 10000 IU.

If the ovaries are abnormally enlarged on the last day of fallitropin therapy, hCG must be withheld during this course of treatment; this will reduce the chances of developing OHSS.

iii) Bromocriptine or Cabergoline

They are taken orally to treat abnormally high levels of the hormone prolactin, which can hinder ovulation.

The dose of Bromocriptine is 1.25mg – 30mg daily in 2- 3 divided doses.

b. Surgical Treatment

Surgery to repair the tubes or remove blockages in the tubes.

Surgery to remove patches of endometriosis.

Surgery to remove uterine fibroids, polyps, or scarring, which can affect fertility.

c. In Vitro fertilization (IVF) Assisted Reproductive Technique (ART)

It is suitable for the treatment of infertility due to endometriosis, sperm antibodies, tubal dysfunction, failure of intrauterine insemination (IUI) cycles, failure of ovarian stimulation cycles with oral or injectable drugs, an age-related decrease of ‘ovarian reserve’, male factor infertility (such as oligospermia), Polycystic Ovary Syndrome (PCO) and idiopathic infertility. It is carried out as follows:

Overstimulation of ovary

Two protocols are used for overstimulation of ovary: Pituitary Down-Regulation Protocol and ‘Flare-up’ Protocol.

Pituitary Down-Regulation Protocol is the most popular protocol and it involves the following steps:

The process usually starts with the onset of a menstrual period.

A full cycle of oral contraceptive is started within the 4 days of the menstrual cycle to prime the ovaries for optimal response.

Seven (7) days before the expected onset of the next menstrual period, a daily SC injection course of Leuprorelin (a gonadotropin-releasing hormone analogue) is started to prevent premature release of the oocytes from the ovaries prior to the oocyte retrieval procedure (and to reduce the level of male hormones to improve the quality of oocytes).

Its administration is continued even after menstruation together with FSH (or a combination of FSH/LH).

The menstrual period will start.

Immediately after the menstrual period begins, FSH (or a combination of FSH/LH) SC injection will be administered daily for 10 days to stimulate the production of multiple oocytes in the ovaries. At the same time, Leuprorelin is still administered.

As FSH (or a combination of FSH/LH) and Leuprorelin administration continues, estradiol and progesterone blood levels are monitored. The ovarian follicles are also monitored using Ultrasound to ascertain whether they have reached the appropriate size.

FSH (or a combination of FSH/LH) and Leuprorelin are stopped.

A single injection of Human Chorionic Gonadotropin (HCG) is administered SC to trigger the final stages of oocyte maturation.

Oocytes are retrieved 36 hours after the HCG injection

The ‘Flare-up’ of ovarian overstimulation Protocol involves the following steps.

The process usually starts with the onset of a menstrual period.

A full cycle of oral contraceptives is started within the 4 days of the menstrual cycle to prime the ovaries for optimal response.

Secen (7) days after stopping the oral contraceptive (or about 3 – 4 days after the start of the 2nd menstrual cycle), Leuprorelin SC single injection will be administered followed by a course of FSH or times FSH administered without Leuprorelin for 4-6 days.

While still administering FSH, monitor the diameter of the follicles and once it reaches 4 mm, administer Clomiphene tablets once daily for three to six days to enhance ovarian stimulation and reduces the likelihood of premature ovulation.

As FSH (or a combination of FSH/LH) and Clomiphene administration continues, estradiol and progesterone blood levels are monitored. The ovarian follicles are also monitored using Ultrasound to ascertain whether they have reached the appropriate size.

FSH (or a combination of FSH/LH) and Clomiphene are stopped.

A single injection of Human Chorionic Gonadotropin (HCG) is administered SC to triggers the final stages of oocyte maturation.

Oocytes are retrieved 36 hours after the HCG injection.

Oocyte Retrieval

This is usually done transvaginally with ultrasound guidance (though it is sometimes done laparoscopically). Under ultrasound guidance, the tip of a thin needle is passed through the top of the vagina into the cul-de-sac. The ovaries are located near the bottom of the cul-de-sac allowing the tip of the aspirating needle to enter the ovarian follicles and aspirate the follicular fluid from them.

The fluid is examined under a microscope to identify the Oocytes.

Fertilization

The semen sample is collected mainly by masturbation, collected stire, washed with tissue culture medium and concentrated for motile sperms, is added to the oocytes at least 6 hours after retrieval of oocytes.

Culture of Embryos

The oocytes and semen are cultured for about 2 to 5 days to allow fertilization. (If the sperm test a possibility of signifcant male infertility, Intracytoplasmic Sperm Injection (ICSI) where a single sperm is inserted into an oocyte)

A fertilized oocyte (zygote) will microscopically show two pronuclei (one from oocyte and another from sperm). In day 2 embryos divides into 4 cells. On day 3 there are 8 cells, and by the 5th – 7th after the oocyte retrieval, the embryos should reach the blastocyst stage (>/= 80 cells).

Embryo Transfer

Fertilized embryo (sometimes it can be more than one) is transferred to the uterine cavity by placing it into the tip of an embryo transfer catheter then passing it through the cervical canal to within 15 mm of the top of the uterine cavity and releasing it gently.

Implantation

Vaginal progesterone capsules are administered to supplement the ovarian progesterone and estrogen production that make endometrium more receptive to the embryo.

A serum pregnancy test is carried out 2 weeks after the embryo transfer and if positive it is followed by Ultrasound examination 2 weeks later to ascertain the implantation site and the heartbeat within the embryo.

Some embryos are stored in liquid nitrogen frozen for transfer in a subsequent cycle.

d. Treatment of Men-related Infertility

Aspiration of sperms from testicles or from the epididymis can be used to treat infertility associated with previous vasectomy, congenital absence of vas deferens, and in cases of low sperm concentration and/or quality.

e. Artificial Insemination (treatment of male infertility)

It can either be intracervical or intrauterine insemination

It is preferred by women who desire to give birth to their own child but the male partner is suffering from male infertility.

Since the timing of insemination is critical for the success of the process, the following parameters are monitored: ovulation, ultrasound, basal body temperature, color and texture of the vaginal mucus and sometimes the softness of the nose of the cervix.

f. A Surrogate Carrier (treatment of infertility when the female of the couple does not produce healthy eggs that can be fertilized)

Woman volunteer is inseminated with sperm from the male partner of a couple.

g. A Gestational Carrier (treatment of cases where a woman produces healthy eggs but is unable to carry a pregnancy to term)

An embryo from a couple is implanted into a volunteer woman (gestational carrier) who will carry the pregancy to term.

h. Egg Donation (treatment of situation where a woman does not produce eggs that can be fertilized)

The donated egg is fertilized by sperm from the woman’s partner, and the resulting embryo is placed into the woman’s uterus.

6. Prevention

  • Effective treatment of STI
  • Treatment of underlying diseases such as hypothyroidism
  • Use of condoms when required
  • Avoid drugs and alcohol
  • Regular medical check-up

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