INFERTILITY: A MUST READ FOR ALL COUPLES

INFERTILITY: A MUST READ FOR ALL COUPLES

It is estimated that about one in ten couples have difficulty in conceiving successfully. The prevalence is high in Sub- Saharan Africa though it is a world wide problem. The number of infertility visits has increased over the past decades. In some cases couples have voluntarily delayed child bearing in favor of establishing careers and may experience an age related decline in fertility.

•      GEOGRAPHICAL DISTRIBUTION OF INFERTILITY
ACROSS THE GLOBE.

Compared to other parts of the world, several countries in Sub-Saharan African have high rates of infertility.

In the UK, estimated 6% of the child bearing age are infertile and in USA, 10%. 

By contrast, most countries in sub-Saharan Africa have prevalence rates of infertility that exceeds 15%. Several countries with high rates of infertility including Nigeria are  Cameroon, Gabon, Democratic Republic of Congo, Burundi, Uganda and Kenya .  

•      The high prevalence of infertility in Africa has profound implication on women’s reproductive health as a result of high premium placed on child bearing in many Africa societies. Infertility is a socially destabilizing condition for couples especially for women and it is the cause of marital disharmony, social ostracisation and physical violence against women. 

•      Available evidence suggests that women suffer more than men as the male factor is not usually recognized as a cause of infertility. In addition there is a large scale misinformation regarding the cause of infertility in Africa. Infertility is often believed to be due to  sundry reason such as witchcraft, dissatisfaction of ancestor, sorcery from unfriendly neighbors and punishment for previous life style (fornication and adultery). Infertile couple frequently consult non-medical sources of treatment like prayer houses, herbalists, traditional healers and spiritualists as a first line measure and as last resort, Orthodox medical help when all these measures fail. Even when they consult the professionals, they tend to go from one practitioner to another and most times combine orthodox with traditional method of treatment.

This health seeking pattern has become more popular in this era of collapsing and expensive health care delivery that is obviously beyond the reach of the average couples in most developing countries like Nigeria.

Irrespective of the physiological intrigues that affect fertility, other factors such as cultural practices e.g. female circumcision, polygamy, incidence of divorce and frequency of coitus have been indicated as factors that can affect fertility .

A thorough diagnostic workup should identify one or more causes of infertility in about 90% of couples. Appropriate therapy will result in pregnancy is about 40% of couples treated 

•      OBJECTIVES

At the end of this unit, the participants should be able to :

Ø Describe the structures and functions of the reproductive system as they relate fertility

Ø Describe the pathophysiology of infertility

Ø Use assessment parameters appropriate for determining the causes and severity of infertility

Ø Describe the management of infertility.  

•      INFERTILITY

DEFINITION:

It is the inability to achieve a pregnancy within a given period of time (i.e. 12 – 18 months) despite regular unprotected intercourse. It is estimated that 60% of married couples having regular unprotected intercourse would achieve pregnancy after 6months of cohabitation. At the end of 12months up 80% would have achieved pregnancy at the end of 18 – 24months, 85 – 95% would have achieved pregnancy.

OVERVIEW OF THE ANATOMY AND PHYSIOLOGY OF THE FEMALE REPRODUCTIVE SYSTEM

•      The female reproductive system consists of external and internal structures. Other anatomic structures that affect the female reproductive system include the hypothalamus and the pituitary gland of the endocrine system.

•      External Genitalia

•      The external genitalia (the vulva) include two thick folds of tissue called the labia majora and two smaller lips of delicate tissue called the labia minora.

The upper portions of the labia minora forming a partial covering for the clitoris, a highly sensitive organ composed of erectile tissue. Between the labia minora, below and posterior to the clitoris is the urinary meatus, the external opening of the female urethra, which is about 3cm (<1.5 inches) long. Below this orifice is a larger opening, the vaginal Orifice or introitus. On each side of the vaginal orifice is a vestibular gland (Bartholin’s gland) a bean sized structure that empties its mucous secretion through a small duct. The opening of the duct lies within the labia minora, external to the Hymen. The area between the vagina and rectum is called the perineum.

•      INTERNAL REPRODUCTIVE STRUCTURES

Consists of the  vagina, Uterus, Ovaries and the Fallopian tubes (Uterine Tubes).

Vagina: The vagina a canal lined with mucous membrane is 7.5 cm – 10 cm long and extends upwards and backwards from the vulva to the cervix.

Uterus

The uterus, a pear- shaped, muscular organ, is about 7.5 cm (3 inches) long and 5cm (2 inches) wide at its upper part. 

Its walls about 1.25 cm, (0.5 inches) thick. The size of the uterus varies, depending on parity (number of viable births) and uterine abnormalities (e.g, fibroid, which are a type of tumor that may distort the uterus). A nulliparous woman (one who has not completed a pregnancy to the stage of fetal viability) usually has a smaller uterus than a multiparous woman (one who has completed two or more pregnancies to the stage of fetal viability). The uterus lies posterior to the bladder and held in position by several ligaments.

The uterus has two part: the cervix which project into the vagina and the larger upper part, the body of fundus which is covered posteriorly and partly anteriorly by peritoneum. The triangular inner portion  of the fundus narrows to a small canal in the cervix that has constrictions at each end referred to as the external os and internal os. The upper lateral part of the uterus are called the cornua. From here the fallopian tubes extend outward and their lumina are internally continuous the uterine cavity.   

OVARIES:

The ovaries lie behind the broad ligaments, behind and below the fallopian tubes. They are oval bodies about 3cm (1.2 inches)long. At birth, they contain thousands of tiny egg cells, or ova. The ovaries and the fallopian tubes together are referred to as the Adnexa.

•      TYPES OF INFERTILITY:

•      Primary infertility: This term is used if the couple has had no previous pregnancy.

•      Secondary infertility: this term is used if the couple has a previous pregnancy irrespective of the outcome of the pregnancy (abortion or ectopic pregnancy).

•      Sterility: this is more absolute or finite and refers to an irreversible state e.g. congenital absence of the vagina.

•      AETIOLOGY FACTOR

The human reproductive process is obviously complex however for the purpose of understanding and evaluation, It can be effectively broken down into its most important basic component parts.

Sperm must be deposited at or near the cervix at or near the time of ovulation, They must ascend into the fallopian tubes and have the capacity to fertilize the Oocyte (male factor).

Ovulation of a mature oocyte must occur, ideally on a regular  predictable cyclic basis (ovarian factor).  

The cervix must capture, filter, nurture and release sperm into the uterus and fallopian tubes (cervical factor).

The fallopian tubes must capture ovulated  ova and effectively transport sperm and embryo. (tubal factor).

The uterus must be receptive to embryo implantation and capable of supporting subsequent normal growth and development (uterine factor).

OTHER CONTRIBUTORY  FACTORS INCLUDE:

-         Unsafe Abortion

-         Sexually transmitted infections (Gonorrhea, Syphilis)

-         Puerperal sepsis

-         Pelvic Inflammatory Diseases

-         Uterine Leiomyomata 

-         Age

-         Environmental factor and lifestyle

-         Smoking

-         Family history of early menopause

PATHOPHYSIOLOGY

In order for conception to occur, the man must produce a sufficient' number of normal, motile spermatozoa in an ejaculate made up of appropriate secretions from the accessory genital glands. Another requirement for conception is the ovulation of an oocyte that is successfully implanted and then ­supported by an adequately functioning corpus luteum. The hormonal events associated with follicular maturation, ovulation, and corpus luteum formation have profound effects on the entire female reproductive system. Fertility is possible only when all parts of this system function so that hormone production is suitable and consistent, follicles develop and nature, ovulation occurs regularly, and optimal conditions exist for the support of a fertilized ovum, e.g. adequate corpus luteum appropriate site implantation, etc.

Transport mechanisms of spermatozoa and semen in human reproduction are complex. Spermatozoa and seminal fluid must both traverse the accessory reproductive ducts of the male and be appropriately ejaculated from the penis. Coitus must occur so that the semen is deposited in or near the cervix.. In the female, initial transport of sperm occurs in the cervical mucus, which is profoundly altered by the presence or absence of estrogen and progesterone, Immunologic incompatibilities may be manifested as abnormalities of cervical transport.

Uterine transport of sperm is a poorly understood phenomenon, The fallopian tubes transport sperm toward the ovary while simultaneously moving ova in the opposite direction, This function is easily disturbed by a prior infection with resultant adhesions or by inflammatory process such as endometriosis.

The endometrial cavity serves as the "incubator" of the fertilized ovum, Endometrial infections or an inability of the endometrium to respond appropriately to endocrine stimulation of the ovary may result in infertility. Distortion of the endometrial cavity by submucous myomas, synechiae, or congenital uterine anomalies may be an uncommon cause of infertility but a frequent cause of pregnancy wastage in the first trimester.

 Endocrine disorders of the pituitary, thyroid and adrenal glands may result in infertility. In most of these disorders, associated anovulation causes infertility. Systemic diseases such as severe or poorly controlled diabetes are associated with decreased fertility, often for reasons that, are poorly understood.

Ø DIAGNOSTIC ASSESSMENT
The diagnostic assessment or tests available for the evaluation of infertility is large. Therefore one must be judicious in his/her choice and use of tests. In Africa many men are often reluctant to seek treatment for infertility . The initial clinical assessment should begin with a thorough history of both partners 
factors to consider include 

Ø The age of the couple

Ø How long they have been married or living together

Ø whether they have had previous partners

Ø If there was any issue from the previous partners and how    long they have been trying to conceive

•      Male factors:
-           Congenital abnormalities – undescended testis
-           Frequency of intercourse – multiple sex partner
-           Prior Paternity
-           Previous Surgery (hydrocele, Hernia, Varicoselectomy)
-           Previous Infection and treatment (Gonorrhea, Orchitis           Mumps)

Past or present illness (diabetes, Hypertension)

•      Drugs and medication (antihypertensive and Steroids, suppresses spermatogenesis).

•      General health (diet and exercise),.

•      Female Factors

•      History of pubertal development (Menarche) age

•      Present menstrual cycle characteristics (length, Duration)

•      Contraceptive history

•      Prior pregnancies and outcome

•      Previous pelvic  surgery

•      Previous infection (PID, STI)

•      Pap smear

•      Drugs and medication

•      General health (diet, weight, exercise patterns).

•      PHYSICAL EXAMINATION

Male: Emphasis is made on the genitalia.

Breast Gynaecomastia

Body: Limited Hair  

Genitalia: The location the urethral meatus. The scrotum is carefully palpated with the individual standing to determine the size and position of the testes.

•      Female

Head: Balding  of Hair

Face: Acne or Hirsutism

Thyroid Gland: Is examined for sign of  hyperthyroidism.

Breast:  Breast is examined for sign of galactorrhoea

Excessive hair on the trunk ie chest, abdomen and supra pubic region and clitoromegaly are suggestive of hyperandrogenism. Visualization of the cervix is done and cervial mucus is examined.  

Uterus: Attention is paid to the position whether It is fixed or mobile. The size and mobility of the ovaries should be determined. The presence of previous scars on the abdomen and masses in the abdomen are important.

INVESTIGATION

The initial evaluation of infertility should be thorough. The various tests should be done systematically. The rationale and procedure of each test should be explained to the couple.

•      Endocrinological investigations

Male:

The following hormones should be measured

FSH      High  FSH and LH may indicate testicular

LH       failure or blockage of the seminiferous duct with normal spermatogenesis occurring in the testis leading to azoospermia.

Testicular failure may result from mumps testosterone levels in blood should be measured. 

•      If FSH and LH are normal in men with azoospermia, it usually indicates obstruction within the seminiferous tubules. This is common sequela  of infectious process  from STI.

Female:
The ovary serves the dual function of steroidogenesis and ovulation so an intact hypothalamic pituitary ovarian axis is necessary for effective performance of both functions.

Estrogen → most important signal in this axis in the early follicular phase, estrogen level is low.

FSH and LH → By a negative feedback mechanism, these 2 hormones are produced at about the mid cycle. There is a surge of LH by positive feedback mechanism leading to ovulation.

The only confirmatory evidence of ovulation is pregnancy

serum progesterone  → this test should be performed at about the 21^st of a 28 day menstrual cycle when maximum production of progesterone by the corpus luteum occurs. A value of 10nmol /ltr is a presumed by evidence of ovulation.   

RADIOLOGICAL  IMAGING

•      Pelvic ultrasonography

   To determine ovulation

   To access uterine cavity for myomas 

•      Hystero salpingogram→ A fluoroscopic study performed by instilling radio opaque dye into the uterine cavity through a catheter to determine the contour of the endometrial cavity and patency of the fallopian tubes. E.g. of abnormal findings includes: Congenital malformation of the uterus, submucus myomas polyps. Salpingitis and tubal occulusion                 

•       Laparoscopy : gold standard for evaluation of tubal faction.

•      Sonohysterosalpingograpy. 

•      Laboratory Studies

Male

Blood tests – VDRL

Semen Analysis: Semen is produced on masturbation after 2-3 days abstinence and examined in the Lab within I hour the following are investigated.

Recommended normal values for semen parameters

Volume                                            2ml or  more

PH                                                      7.2 – 7.8

Sperm concentration                  20 x 10⁶ sperm/ ml or more

Total sperm count                       40 x 10⁶ sperm/ml or more

Motility                                            50% or more with forward progress

Morphology                                   30% or more  with normal morphology

Viability                                           75%  alive

Hormonal assays: FSH, prolactine, LH, Testosterone, Progesterone and TSH levels. Progesterone level of 13nmol/ltr shows evidence of ovulation.

Post coital test:  A specimen of aspirated cervical mucus from the female partner is examined at the fertile time of the cycle within 6hrs of intercourse .

The ability of the sperm to enter the mucus can be observed. The test gives confirmation that effective intercourse is taking place.

Other investigations includes Basal Body Temperature BBT.

Endometrial Biopsy: to show secretory endometrium that has maturity that is compatible with the day of endometrial sampling.    

 

•      MANAGEMENT OF INFERTILITY (MEDICAL)

Male Factor:
The Treatment of male infertility is difficult in Africa but generally depends on the possible cause(s) of the problem when no definite cause is found especially when testicular failure and obstructive Azoospermia have been excluded. Sperm count and motility may be improved by counseling  on;

•      Dietary and behavioural modification

•      Cessation of smoking and alcohol consumption

•      Avoidance of prolonged sitting at work

•      Weight reduction

•      Wearing of loose boxers

•      Semen culture is done to exclude infection.

If sperm count is low → mesterolone (a mild androgen) is given to increase sperm count and motility.

Steroid therapy: this is given and beneficial in  patients with antisperm antibodies in seminal plasma and serum.

Prednisolone 5mg tds dly × 6months can be tried

Artificial insemination: insemination into the vagina, cervix or directly into the uterus using partners semen is done.

FEMALE  FACTOR

·        Cervical factor: poor cervical mucus should be treated with estrogen given few days before ovulation this may enhance the cervical mucus. If there cervicitis it should be treated appropriately.

·        Ovulation factor
if there is annovulatory menstrual cycle, ovulation may be induced with clomiphene citrate 50mg tablet are given from day 2 to day 6 of the cycle.

The dose is increase by 50mg every cycle if no pregnancy occurs till a maximum of 150mg is reached. It is necessary to use estradiol assay or cervical mucus scoring or ultra sonograpy to monitor the induction of ovulation to prevent hyper stimulation syndrome.

Hyperprolactinaemia another leading cause of anovulatory infertility in Africa is treated with the dopamine agonist bromocryptine.

It should be commenced at a dose of half a tablet at night (1.25mg) and increased gradually every 3-5days to 2.5mg at night and then 1.25mg in the morning with 2.5mg at night until the daily dose is 7.5mg in 2 to 3 divided doses. Most patient experience a fall in prolactin levels within a few days of commencement of treatment and ovulation occurs within a few weeks.            

•      The major problem of this drug is the high incidence of side effects which include nausea, vomiting, headache and postural hypotension .

SURGICAL  MANAGEMENT

Male Factor:

Vaso-va sostomy: This involve excision of the portion of the vas-deference blocked as a result of infection and then an anastomosis.

Female Factor:

•      Myomectomy: This is the surgical removal of benign tumors of the uterus(fibriods).
 Tubal surgery or resection or anastomosis
 intrauterine insemination:
 Invitro fertilization/embryo transfer (IVF) procedure.
-           Ovulation is induced using drugs
-           Ovum or ova recovered using ultra sound guidance
-           Embryo transfer is done 2-3 days later after the zygote have                       reached 4 or 8cell stages.

Gamete Intrafallopian Transfer (GIFT)

Used, when there is cervical barriers to conception. At least one fallopian tube must be patent and sperm quality must be good.

•      Procedure;
Ovulation is induced.
Ovum or ova are harvested and aspirated into a catheter with fresh sperm and than placed in distal end of the fallopian tubes.

·        Intra cytoplasmic sperm injection (ICSI)

·        Ovum donation

·        Surrogacy

·        Adoption

NURSING  MANAGEMEN T OF INFERTILITY

•      NURSING MANAGEMENT OF INFERTILITY USING GORDON’S FUNCTIONAL TYPOLOGY

HEALTH  PERCEPTION  PATTERN

            Get history of patient’s problem (infertility), how long they have been married, any issues, past menstrual cycle, length of cycle and regularity.

Ø Previous treatment sought for and where it was sought for; orthodox or traditional treatment.

Ø History of drugs or herbs and concoction taken.

Ø Life style, job description and place of work. Long distant drivers.

•      NUTRITIONAL / METABOLIC PATTERN

•      Find out previous weight (Anorexia nervosa or obesity).

•      Smoking of cigarette, alcohol intake

•      Assess for good skin, tugor and elasticity

ELIMINATION PATTERN:

·        Obtain history of pattern of elimination bowel and bladder (frequency, consistency or urgency, volume) constipation, diarrhoea .

ACTIVITY PATTERN 

v  Note fatigue due to anaemia or obesity

v  Assess ability to carry out ADL

v Type of work (sedentary life style) e.g. long distant drivers, or CEO in the office.

SELF PERCEPTION/ SELF CONCEPT PATTERNS

Find out how patient feels about self. Does he feel positive or guilty about self? previous life style, Is he / she blaming self or partner?

Assess feeling of self worth, value of life

  

ROLE RELATIONSHIP PATTERN

•      Relationship with spouse, parents, siblings and in-laws

•      Assess nature of interaction with significant others (i.e) warm, lonely or evidence of intimacy with others.

SEXUALITY OR REPRODUCTIVE PATTERN

q  Marital History

q Any children, number of children and their sexes

q Sexual pattern find out how many times they have sexual intercourse in a week.

q Is he polygamous or a bigamist (multiple sexual relationships)

q Is there any limitation condition has placed on marital relationship as relates to sex.

q What do they feel about the problem? 

COPING / STRESS TOLERANCE PATTERNS

ü  Assess for anxiety

ü Family support or denial

ü Is there tension, Aggression at love lost

VALUES/ BELIEF PATTERNS

Find out religious affiliation about condition and remedies available eg. Gift, zift, ICSI.

What value does he place on life generally. Find out any special need for religious ritual, practice or personality.

    

PATIENTS EDUCATION AND LIFE STYLES MODIFICATION

A patient  who has this condition most times is overwhelmed by emotions especially on seeing friends, family members who show concern or at slight misunderstanding may refer to his/her being unable to have a child of his own as being the cause of insults or let down.

The care provider should then be on the alert on the manner and way he/she relates to the patient as this may alleviate or aggravate already tensed situation.

The patient should be advised to avoid self medication, Smoking, and alcohol consumption, using tight inner wears, long distance driving and job specification modification etc.

PREVENTION OF INFERTILITY

A large proportion of the causes of infertility in Africa can be prevented. A comprehensive strategy using primary, secondary and tertiary perventive methods is advocated.

Primary prevention: prevention of causes that can lead to infertility and they include:

o   STI, post abortion infection and puerperal infections. Thus the primary prevention of infertility ought to be carefully integrated into community education on behavioural change, modification on sexual practices, effective contraception and effective ad qualitative maternity care service.

Secondary prevention: involves the early recognition and treatment of sexually transmitted  diseases and the prompt treatment of abortion and puerperal infection. All cases of spontanous and induced abortion should be promptly treated and  antibiotics administered to prevent pelvic infection and future infertility.

•      Tertiary Prevention: include the use of methods to mitigate or cushion the effects of infertility on couples. These methods include 

Systematic counseling of affected couples, treatment with convenient methods eg IVF, GIFT, ZIFT

  

TABULAR REVIEW OF PREVENTION OF INFERTILITY

Male	Female	Both
Environment
Reduce estrogenic Pollutants Protect workers in chemical industries	Avoid unwanted Pregnancies and TOPs	Avoid STI Use contraceptives Avoid multiple sex partners
Physiological undescended testes and early orchidopexy avoid injury to vas and testicular vessels mumps vaccination should be given for orchtis and varicocelectomy  for varicoceles	Fibroids should be removed. Tubal blockage should be resected or anastomed hyper prolactinaemia and should be treated with appropriate drugs. Anovulatory cycles PIDs STIs should be properly treated	They should be treated together in case of STIs

Identified Nursing Problem

1.     Anxiety  and fear related to unknown procedure and treatment outcome as evidenced by restlessness.

2.     Deficient knowledge on the process of ovulation, pregnancy, and sexual relationship as evidenced by asking too many questions.

3.     Low self esteem related to inability to conceive as evidenced by expressions of grief.

PLAN OF NURSING CARE: THE PATIENT WITH INFERTILITY

Nursing diagnosis: Anxiety  related to unknown procedure, treatment and prognosis evidenced by restlessness

Goal: Reduce stress and improve ability to cope

S/no	Date	Time	Nursing diagnosis	Nursing objective	Nursing  order	Scientific  rationale	Evaluation
1	14/10/13	12:10pm	Anxiety related to unknown procedure, treatment and prognosis evidenced by restlessness	Anxiety will be allayed stress reduced and there will be improved ability to cope throughout the period of  care	Obtain health history especially her level of understanding of health problems (2)  Provide education about diagnosis  and treatment plan (3) Assess psychological  reaction to diagnosis/ prognosis	Helps to clarify inform and facilitate patients understanding and coping. (2) Helps the patient to understand diagnostic tests and treatment plan (3) Provides clues in determining appropriate measures to facilitate coping	Throughout the period of nursing care she appeared relaxed and verbalized allayed   anxiety as well as demonstrated a good understating of condition  tests and prognosis

S/no	Date	Time	Nursing diagnosis	Nursing objective	Nursing  order	Scientific  rationale	Evaluation
2	14/10/13	12:10pm	Deficient knowledge on the process of ovulation, pregnancy  and sexual relation as evidenced by asking too many questions	Patient will demonstrate good knowledge and understanding of the process of ovulation.  Pregnancy and sexual  relation within the period of Nursing care	Encourage communication with the patient and give a hastening ear. Review the anatomy of the involved organs  and systems in a way she can understand. Be specific in selecting information that is relevant to the patients particular treatment plan. Include her partner while teaching  specific topics	This is designed to establish  rapport and trust Orientation of one’s anatomy is basic to understanding its function. The specific information will help in better understanding  of problems. This provides bond between the couple and it is strengthened with new appreciation and support for each other	She demonstrated a good knowledge and understanding of the process of ovulation, pregnancy   and sexual relation before  the end of nursing care

S/no	Date	Time	Nursing diagnosis	Nursing objective	Nursing  order	Scientific  rationale	Evaluation
3	14/10/13	12:10pm	Situational low self esteem related to inability to  conceived  evidenced by expression of  grief.	Patient will improve and maintain high self esteem throughout period of care	Assess patent’s  and family’s responses to condition and treatment ` -Assess relationship of patient and significant others eg family members co-workers, church members -Identify coping patterns of patient and family member -Encourage open discussions about condition e.g role changes, lifestyle sexual changes etc. - Explore and discuss alternative ways of conception. - Discuss role of giving and receiving love, warmth and affection	Provides information about problems encountered by patient and family in relation to condition. -Identifies  strengths  and supports of patient  and family thereby increasing self esteem. -Coping patterns may be helpful even now. -Help patient to identify concerns and steps necessary to deal with them. -Alternative ways may be acceptable. -This will help maintain high self worth and esteem	Patient maintained high self esteem throughout the period of care

CONCLUSION

There is high rate of infertility in Africa, however with the current recognition of the enormous social problem associated with infertility the view is rapidly changing especially with the broader  perspectives on women’s health espoused in Beijing conference for women. Women's reproductive rights are now central in efforts to promote reproductive health and social development and no single issue illustrates the abuse of woman’s reproductive right more eloquently than infertility thus I recommend that national and international policy makers and agencies concerned with health should recognize infertility as an important area requiring focused interaction and programming.

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   Speroff L, Glass, R.H, Kase, N.G, eds. (2002) Clinical Gynecologic

                   Endocrinology and infertility, 8^th ed, William Wilkins   

                   Publishers, Baltimore. 

   WHO (2005) Epidemiology of infertility. Report of a WHO scientific

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