Infertility

Table of Contents

Infertility is the inability of a couple to conceive or to get a child after one year of regular coitus without having used any form of contraception.

Infertility refers to failure to conceive inspite of regular unprotected sex during the child bearing age that is 15-49 years without any contraception for atleast one year.

Types of infertility

Primary infertility: It is inability to conceive in a couple that has had no previous pregnancies.

OR Is the term used for a couple who have never achieved a pregnancy at any time after 1 year of unprotected sex.

Secondary infertility: It is where one has ever conceived but then stops to produce when she is not on any method of family planning.

OR Refers to a couple who have previously succeeded in achieving at least one pregnancy even if this ended in spontaneous abortion being unable to conceive again.

Causes of infertility

In males

Depression
Release of immature sperms or abnormal or little or slow in movement.
Poor or failure to ejaculate
Extreme heat: An increase in temperature of the testes from a prolonged fever or exposure to excessive heat can greatly reduce sperm count, vigor of sperm movement and it increases the number of abnormal sperms in semen.
Hydrocele ie excessive collection of the fluids in the scrotum. This prevents adequate production of sperms.
Varicocele ie varicose veins of the scrotum: This abnormality may prevent proper supply and drainage of blood from the testes thus rising the temperatures and reducing the rate of sperm production. It also affects ejaculation.
Drugs of amoebiasis called amoebicides, anti-hypertensives like aldomet and diabetic drugs cause failure in erection.
Diseases like mumps cause a condition called orchiditis (inflammation of the testes)
Hormonal imbalance.eg inadequate production of testosterone hormone may result into immature sperms.
Degenerative changes in sperms. This can be caused by nitrofurantoin.
Excessive smoking and alcohol consumption.
Obesity
Retrograde ejaculation: This is ejaculation into the bladder. It is assessed by urinalysis after ejaculation
Exposure to toxic chemicals or radiations affects the spermatogenesis.

GENETIC FACTORS
Klineflters syndrome and Turners syndrome.

KLINEFELTER’S SYNDROME: A syndrome consisting of gynaecomastia, testicular atrophy, azoospermia and infertility.
Testicular atrophy is a result of peritubular fibrosis which commence in childhood and progresses until all seminiferous tubules are replaced by fibrous tissue. Patients have 47 chromosomes
instead of 46 with an extra X chromosome so that the sex chromosome constitution is XXY instead of XY. Loss of a Y chromosome leads to a body which is feminine.
b) TURNER’S SYNDROME: It is caused by either the absence of or an abnormality in one of the two X chromosomes. Classical turner’s syndrome is a complete deletion of one X so that the karyotype is 45XO. They are females but have ovarian failure, widely spaced nipples, cardiovascular problems, squints, hypothyroidism and diabetes mellitus hence infertility. In adult life, they have problems of
oestrogen.

Causes/factors in females

Are best discussed under the following headings;

– Defective Implantation
– Endocrine Disorders
– Ovarian Disorders
– Defective Transport
– Physical / Psychological Disorders
– Systemic Disorders

DEFECTIVE IMPLANTATION

Major cause is tubal blockage due to PID (in Uganda especially). This contributes to 60 – 70%.

Salpingitis caused by infection after abortion or delivery by gonorrhoea, chlamydia or tuberculosis or by pelvic peritonitis from acute appendicitis may damage the tubal epithelium and in severe cases bring about tubal blockage. This mostly occurs at the outer end of the tube where the fimbriae adhere together but is also seen in the very narrow, interstitial part of the tube.
When the tubes are not completely blocked, fertilization of the ovum may still take place but because of the damage to the ciliated epithelium the fertilized ovum may not be carried down the tube to the uterus and an ectopic pregnancy results.
Abnormalities of the uterus. Some people are born with no uterus or with a bicornuate uterus or Didelphys uterus with 2 horns).
Tubal factors. eg tubal blockage due to adhesions resulting from STIs.eg gonorrhea
Uterine fibroids (gross) causing an irregular implantation surface.
Severe inflammation of the endometrium called uterus synechiae /endometritis.
Intrauterine adhesions after myomectomy
Over curreting of the uterus or surgery of the uterus i.e. Hysterectomy, Stenosed Cervix due to trauma or injury due to dilatation and curettage. May be acquired or congenital Gynaeatresia i.e. a very small hole with a blind end of the
vagina.
Endometriosis– A condition where patches of the endometrial like tissue develop outside the uterine cavity in abnormal locations such as ovaries, fallopian tubes and abdominal cavity. Can grow
with hormonal stimulation causing pain, inflammation and scar tissue hence infertility.
Trichomonas vaginalis (evidence of cause in Zambia).
Use of barrier contraceptives e.g. condoms, IUDS and Spermicides
Septate vagina and rigid hymen
Congenital absence of fallopian tubes

ENDOCRINE DISORDERS

Hormones, Pituitary and Ovarian Inefficiency. There may be alteration of hypothalamic function resulting from stress (resulting in altered dopamine or noradrenaline transmission)
Or
Alteration of hypothalamic function due to some drugs e.g. rawolfia, phenothiazines or metaclopramide
Or
Weight loss or excessive weight gain causes unstable cerebrum and
Hypothalmus
– May be a pituitary tumour which leads to production of excessive prolactin hormone hence causing Anovulation.
These tumours are usually micro and macroadenomas which cause hyperprolactinaemia. Elevated levels of prolactin levels are normal during lactation and anovulation ensues as a result but if not
lactating causes infertility.
Thyroid function: Changes in thyroid function (hyperthyroidism or hypothyroidism) or in adrenal function (cushings syndrome or congenital adrenal hyperplasia) result in anovulation.
Age – menopause. Fertility declines with age. Postponement of childbearing because of career can be a problem.

OVARIAN CAUSES

Ovary malfunction: Absence of FSH receptors in the follicle leads to failure of the ovary to respond to gonadotrophins (resistant ovary syndrome) or there may be disturbance in the interaction between FSH and the follicle. This disturbance may result in abnormal enzyme reaction- anovulation will result and the ovary becomes
multicystic hence (polycystic ovarian syndrome). Failure of ovulation results in absence of secretory changes in the endometrium and the cervical mucus remains thick and impenetrable by the sperm.
No eggs or no follicles in the ovary. Can be congenital.
Premature menopause
Surgery i.e. removal of the whole ovary mistakenly as in surgery of the ovary.
Infection such as mumps can destroy the ovary substance
PID = (adhesions (Ashermans Syndrome).
X-Ray Exposure: Chronic or excessive exposure to radioactive substances or x-ray. These could damage the ova.

DEFECTIVE TRANSPORT

Allergy to the man’s sperms/cervical hostility – This is a condition in which the cervical mucus is unreceptive to spermatozoa either preventing their progressive advance or actually killing them. It may be due to infection or to the presence of sperm antibodies.
Vaginal Ph ( acidic destroying the motility of the sperm)

PHYSICAL/ PSYCHOLOGICAL CAUSES

Other conditions preventing union of ova and sperm in female are;

Dyspareunia (painful or difficult sexual intercourse experienced by a woman due to psychological or physical factors) and vaginismus.
Physical abnormality of the reproductive organs ie retroverted uterus.
Psychological factors like stress and depression.
Wrong timing of sexual intercourse during infertile periods.

SYSTEMIC CAUSES

Systemic diseases e.g. Diabetes Mellitus, hypertension and renal failure

Treatment

Treat according to the cause.

Prevention

Stop smoking
Reduction of alcohol consumption
Proper diet
Meeting at the right time
Reduction in stress and tension
Counselling
Artificial insemination

Complications

Depression
Divorce
Sexual immorality
Polygamy

Conditions that should be fulfilled for implantation to occur.

There should be 2 lovers
Get unprotected coitus without contraception and both should actively get involved.
Should be using the right sexual route – vagina for a woman with a penis (male).
Should be within the age of conception, 14 to 49 years.
There should be release of healthy semen containing normal spermatozoa.
Normal, healthy ova must be released from the ovary.
The ovum must unite with the sperms to be fertilized.
The fertilized ovum must be implanted in the uterus.
NB: The term sterility should be used only when there is no treatment possible to enable a couple to conceive (achieve pregnancy) such as when a man has no testes or a woman lacks a uterus.

GENERAL INVESTIGATIONS

All couples who complain of infertility should be investigated but the length to which the investigations should be carried out will vary.
Both partners should be seen for initial interview.

EVALUATION IN WOMEN(FEMALES)

History

Menstrual history i.e. menarche and length of menstrual periods.
Previous gynecological history i.e. any previous contraceptive and its outcome, History of dilatation and curettage, salpingectomy etc.
Any History of abortions or History of suggestive Pelvic inflammatory diseases.
Previous obstetric history i.e. previous pregnancies and number of children fathered by this
man.
History of pelvic infection.
General state of health and nutrition.
Age of both man and woman. Above 50 in female is considered as menopause.

Her weight

Very lean thin and very obese woman have a problem. In the obese the ovary cannot secrete enough oestrodiol so they secrete more of oestrone hormone.
Very thin – amenorrhoea – infertility.

Sight of the Woman

If one has a pituitary tumor she can’t see objects on the side.

Check for excessive prolactin
Check for hair distribution

i.e. pubic hair and general body hair distribution. If a lady has virilism – have Androgen – more masculine

Vaginal Examination

On V/E check for normality of the vagina confirm with ultra sound.

Hormonal Investigations

In a 28 cycle check for progesterone levels on day 21 to check for ovulation.

Ovulation

Serial ultra sound to see ovulation

FSH and LH

Check FSH and LH especially in people with premature menopause or removal of the ovary.

Hysterosalpingogram
Post coital test to check whether the woman allergic to sperms.
Polycystic ovary common in the Europeans

SPECIAL TESTS

BASAL BODY TEMPERATURE
Ovulation is confirmed by the lady taking her oral temperature every morning on waking up and records it on a special temperature chart. This must be done before rising or starting any activity.
A rise in the basal body temperature of about 0.5 degrees C in the last 14 days of the cycle indicates that ovulation has occurred continued x 6
/12.

EXAMINATION OF CERVICAL MUCUS
Examination of the cervical mucus in the midcycle will reveal characteristic changes if ovulation has occurred.
Ovulatory mucus is clear copious and can be drawn out into a fine thread (spinnbarkeit).
On drying it crystallizes out into the characteristic fern pattern.
A sample of blood is taken off 1 week before a period is expected I.e. Day 21 or of a 28 day cycle a progesterone level of more than 20 mmol confirms that ovulation has taken place.

HISTOLOGY
Histological examination of a premenstrual endometrial biopsy it will show secretory changes in the glands after ovulation.

LAPARASCOPY
This is a tubal patency test. It’s a premenstrual laporascopic exam of the tubes combined with injection of a dilute solution of methylene blue through a tightly fitting cannula placed in the cervical canal. The
uterus can be seen to be distended by the dye and if the tubes are patent they fill with dye which finally spills from the distal ends. Distal block is recognized if there’s no spill and medial block can be inferred if no dye enters.
NB: Pregnancy should be first ruled out.

TUBAL INSUFFLATION
It is an unreliable method where carbon dioxide is used, passed via the vagina to the uterus. If there’s a problem in the uterus or tube the gas will be felt on Auscultation. An Xray is later done to Rule out blockage or no blockage.

HYSTEROSALPINGOGRAM
Here an opaque radio aqueous solution through the cervix to the uterus and tubes is done under radiographic control the test is performed in the 1st 5 to 10 days of the cycle after menstrual bleeding has ceased but before Ovulation has occurred. An Xray is taken. Free spill of dye from the distal ends of the tubes proves patency and no spill indicates site of blockage.

POST COITAL TEST (HUHNERS TEST)
Carried out at time of ovulation or 1 to 2 days before ovulation. 2-8 hours after unprotected intercourse, the cervix is exposed by a bivalve speculum and a sample of cervical mucus is withdrawn from the endocervical mucus with a wire loop or pipette placed on a warm slide and covered with a coverslip.
The number of progressively motile sperm in a number of high power fields is examined. Normally a large number of active sperm will be seen.

PROLACTIN TESTS
When prolactin level is higher than 800 m/u/l computerized tomography of the pituitary fossa is indicated to exclude a prolactin producing pituitary adenoma.

ENDOMETRIAL BIOPSY
It is done 10- 12 days after ovulation.

TRANSVAGINAL ULTRASOUND (TVS)
Contraindications
– Presence of suspected pregnancy
– Presence of cervical erosion
– Presence of infection
– Serious heart and lung diseases.
– Patient in Menstrual periods or with Dysfunctional Uterine Bleeding
Risks
– Embolism
– Ascending Infection

EVALUATION IN MAN (MALE)

Obesity – Diabetes Mellitus – Hypertension – Infertility
Hair distribution and development of genitalia
For undescended testis – Operation before puberty is done
Check breasts for enlargement, shows increased oestrogen
Testes, size and situation.
Decreased Androgen shows infertility.
Blood test to evaluate FSH and LH levels.
Sperm count/ seminal fluid analysis normal count is 20 million/ml. If below 10 million there’s a problem (Oligospermia)

NORMAL FINDINGS

Normal volume ≥ 2ml or 2.5ml
pH- 7-8
Total sperm count- more than 20 million/ml
Liquefaction- complete in 1 hour
Motility ≥ 50% with forward motility
Morphology – 30% or more – with normal shape
Concentration ≥ 20 million/ml

Azoospermia: Lack of sperms in semen
Oligospermia: Little or few sperms less than 20 million/ml
Asthenospermia: Decreased motility of the sperms
Teratospermia: Excessive abnormality of the sperms in semen.

TREATMENT IN GENERAL IN WOMEN

CHEMOTHERAPY

In Anovulatory Infertility, stimulate the ovary by giving Clomiphene Citrate (Clomid)
Dosage
> 50mgs daily for 5 days of onset of menstruation preferably on the second day or at any time if the cycles have ceased. If ovulation does not occur a second course of 100mgs daily for 5 days may
be given starting as early as 30 days after the previous one,
In general 3 courses of therapy are adequate to assess whether ovulation is obtainable.
> Clomiphene induces ovulation by stimulating the Hypothalamic pituitary system.
Key issues to note: This treatment often results into multiple pregnancy because the dose of the drug is difficult to adjust.
Side effects
> Visual disturbance
> Abdominal discomfort
> Headache
> Insomnia
> Ovarian by hyperstimulation
> Hair loss
> Breast tenderness
> Depression
> Hot flushes
> Abnormal uterine bleeding
> Inter menstrual spotting
> Endometriosis
> Dizziness
> Nausea and vomiting
> Menorrhagia
Give Tamoxifen 20mgs daily on days 2, 3, 4 and 5 of the menstrual cycles. Dose may be increased to 40mgs the 80mgs.
If patient has hyper prolactanaemic infertility give Bromocriptine (also called parlode lactodel, dopagon or Brameston).
It is used to inhibit synthesis of release of prolactin by the pituitary gland.
Dosage
Initially 1.25mgs at bed time which is increased gradually to the usual dose of 2.5mgs 3 times a day with food. Increased if necessary to a maximum dose of 30mgs daily.
Side Effects
> Nausea
> Headache
> Nasal congestion
> Fatigue
> Dry mouth
> Diarrhea
> Constipation
> Drowsiness
> Hypotension
> Dizziness
> Abdominal cramps
Drug Interactions
1. Erythromycin may increase plasma concentration hence risk of toxicity of Bromocriptine.
2. Bromocriptine is antagonized by antipsychotics and domperidone plus metoclopramide.
3. In patients with hypothalmic dysfunction leutinising hormone administration is given to induce a pituitary response.
Dosage
10-25 micrograms released via a syringe pump every 90 minutes. It’s given intravenously or subcutaneously.
The treatment is continued throughout the menstrual cycle
The success rate of 60-70% has been shown.
Tubal Blockage
Surgery is performed in an attempt to unblock them and remove adhesions. Success rate is low.
– Salpingolysis
This is when peritubal adhesions around the ampullary ends of the tubes are divided and
function restored.
– Salpingostomy
This is when the fimbriae are turned back to produce a new opening of the tube.
– Tubal Anastomosis and Repair
This is usually done when the blockage is at the Isthmus. The blocked segment is incised and cut ends anastomosed.
If interstitial portion, re-implantation after dividing the tube close to the uterus is done and coring out the blocked segment is carried out.

Anovulatory Infertility

Synthetic Human Chorionic Gonadotrophin hormone may also be given. It is identical in action to leutinizing hormone and can trigger ovulation. Intercourse should be advised around the time of administration for successful results.
Human Menopausal Gonadotrophin HMG (Pregonal) or Pure FSH (Metrodin) may be used if clomiphene has failed.
Uterine, cervix or vaginal problems are corrected. If uterine fibroids (Myomectomy).

TREATMENT IN MALE

Human Gonadotrophin Therapy give clomiphene citrate to stimulate sperm production.
Testosterones to stimulate sexual desire. It should not be given in cases of impaired spermatogenesis
Surgery Measures
> Is done to relieve reproductive tract obstruction.
> If inguinal hemia – hemia repair is done.
> If vericocele – surgical ligaturing of the internal spermatic vein.

OTHER CONSIDERATIONS FOR BOTH PARTNERS
In Vitro Fertilization
Robert Edwards received the noble prize in Physiology for development of IVF. It was developed in 1978. IVF needs a healthy ova, sperms that can fertilize it and a uterus that can maintain pregnancy. Is an infertility treatment of women who are unable to conceive naturally. An ovum is obtained from the woman herself or it may be donated put in a test tube and mixed with the sperms of the husband or donor sperms later the embryo is implanted in the uterus to grow. The treatment often results in multiple pregnancies because many fertilized ova are transferred to the woman to increase the likelihood of implantation.
IVF can be combined with surrogacy (egg donation) and pre implantation genetic diagnosis (PGD) to rule out presence of genetic disorders (similar to a general test called pre implantation genetic haplotyping)

METHOD
Collection of contents from the fallopian tubes or uterus after natural ovulation is done, and then mixed with semen and re inserted into the uterus.

ADDITIONAL TECHNIQUES to make chances of conception higher are used:

Ovarian hyper stimulation by GnRH agonist and FSH to retrieve multiple eggs.
Ultra sound guided transvaginal oocyte retrieval directly from the ovaries by an injection of HCG (the trigger shot)which acts as an analogue of luteinizing hormone is done. Ovulation is expected between 38 and 40 hours where as egg retrieval is between 34 and 36 hours prior to follicle rupture. This should be done with caution to prevent hyper stimulation ovarian syndrome which could lead to ovarian disorders thereafter.
Egg and sperm preparation by sperm washing to remove excess semen and purification from microbes and viruses .i.e. HIV is done.
Finally selection of the resultant embryos to be transferred to the uterus is done.
ICSI Intra cytoplasmic sperm injection may be performed alongside IVF. It may assist in male infertility where there is a defect in sperm quality or where sperms have difficulty penetrating the egg or where sperm numbers are very low. Sperm cells are injected directly into the egg cell before implantation in the uterus.

Surrogate Parents
In the absence of a uterus, the woman’s ova may be fertilized with the husbands sperms as above and later the embryo implanted in another woman’s uterus for her to carry the pregnancy for the couple.
As soon as the baby is born the surrogate mother hands over the child to the rightful parents.

Adoption of Children
If still eager to have children, they can visit an adoption centre fill in forms and apply for adoption of a child of choice.

Artificial Insemination by a Sperm Donor (AID)
This is considered when a male partner is infertile. The semen of a fertile donor is used for a woman who is potentially fertile to achieve pregnancy.

NURSING DIAGNOSES

Anxiety and fear related to unknown procedures, treatment and outcome evidenced by patient’s verbalization.
Low self esteem related to inability to conceive evidenced by low mood, negative attitude and social isolation.
Knowledge deficit related to the process of ovulation, pregnancy and sexual relationship evidenced by inadequate verbalization of correct sexual behavior information.
Knowledge deficit related to sexual anatomy and physiology/ causes of infertility evidenced by inadequate verbalization of related information.

INFERTILITY