SubfertilityBy: jwan Abdullah

Ushana shamshon

Fertility

Fertility is the natural capability of producing offspring.

Women who are fertile experience a natural period of fertility before and during ovulation, and they are naturally infertile during the rest of the menstrual cycle.

Depends on factors:

Nutrition

Sexual behavior

Culture

Endocrinology

Timing

Emotions

What is Subfertility?

What is Subfertility?

Subfertility is defined as the failure to conceive within 1 year of unprotected regular sexual intercourse.

In the general population, conception is expected to occur

in 84% of women within 12 months and in 92% within 24

months

Primary and Secondary Subfertility

Primary

Couples who have had NO previous conception.

Secondary

Difficulty conceiving after already having conceived (and either carried the pregnancy to term or had a miscarriage).

Data from population-based studies suggest that 10–15% of couples in the Western world experience infertility Half of them (8%) will subsequently conceive with out the need for a specialist

Approximately 50 per cent of couples will conceive

after receiving advice and simple treatment, but the

remainder require more complex assisted conception

techniques, and 4 per cent of couples will remain

involuntarily childless.

The most important factor in determining fertility is the age of the female partner, with fertility reducing rapidly in women over 35 years of age

Conception

For a woman to conceive, certain things have to happen:

Intercourse must take place around the time when an egg is released from her ovary.

The systems that produce eggs and sperm have to be working at optimum levels.

And her hormones must be balanced.

Factors affecting fertility in women.

1. Ovulation Disorders

2. Tubal Damage

3. Age (>37 years)

1. Reduce chance of a spontaneous conception.

4. Low coital frequency or inappropriate time of intercourse to ovulation.

5. No previous pregnancy

6. Smoking

7. Malnutrition

1. Obesity

2. Underweight

8. Endometriosis, Fibroids, PID (Pelvic Inflammatory Disease).

Table 45.1 Diagnostic categories in infertility

Primary (%) Secondary (%)

Anovulation 20 15

Male 25 20

Tubal 15 40

Endometriosis 10 5

Unexplained 30 20

Ovulation Disorders

Arise due to defects in the hypothalamus, the pituitary or the ovary.

Factors that disrupt the release of GnRH:

Stress and psychological disturbances.

Weight change.

Systemic Diseases and lesions of the hypothalamus.

Hyper and Hypothyroidism.

Lead to Anovulation and Ammennorrhea

Hyperprolactinaemia (as seen in women with

a prolactinoma), renal failure, hepatic dysfunction

and phenothiazine medication impair the pulsatile

release of GnRH, leading to anovulation.

Polycystic Ovarian Disease

Most commonest cause of anovulatory infertility accounts for over 75% of all women with anovulation (Adams et al. 1986)

.

Symptoms:

Menstrual Cycle Disturbances.

Obesity

Hirsutism

Acne and INFERTILITY!

Diagnosis:

Low Sex Hormone binding Globulins.

Ultrasound Appearance of an enlarged ovary with multiple sub capsular follicles and a dense stroma.

namely the presence of two out of the following three criteria:

1 Oligo- and/or anovulation;

2 Hyperandrogenism (clinical and/or biochemical);

3 Polycystic ovaries (The Rotterdam ESHRE/ASRMsponsored

PCOS consensus workshop group, 2004).

Other aetiologies of hyperandrogenism and menstrual

cycle disturbance should be excluded by appropriate

investigations, The morphology of the polycystic ovary, has been redefined as an ovary with 12 or more follicles measuring 2–9 mm in

diameter and increased ovarian volume (>10 cm3) on transvaginalultrasound.

PCOS Treatment for subfertility

Diet & Exercise

PCOS diet book by Colette Harris

Clomid* – Anti-oestrogen

days 2-6 of cycle

with follicle tracking

Metformin

start at 250mg od increase to max 500mg tds

GnRHa*

Laparoscopic ovarian drilling

* Risk of OHSS

Premature Ovarian Failure.

Total failure of the ovaries in women under the age of 40 years.

Characterized by:

Amenorrhoea.

Raised FSH.

Decreased Estradiol.

Linked to genetic causes.

Sex Chromosome abnormality.

Acquired from damage by viruses and toxins.

Pelvic Surgery, irradiation or autoimmune.

Tubal Dysfunction

Impaired oocyte pick-up mechanisms by the fimbriae or damaged tubal epithelium.

Tubal Damage following:

Pelvic Infection.

Endometriosis.

Pelvic Surgery

Pelvic sepsis following appendicitis or peritonitis.

STD’s – Leading to tubal damage.

Chlamydia trachomatis

Gonocci

Disorders of Implantation

Defects related to endometrial development and maintenance.

Submucous Fibroids - benign or non-cancerous tumors found in the muscular wall of the uterus distorting the endometrial cavity.

Endometriosis

Endometriosis is most simply defined as the presence of endometrial surface epithelium and/or the presence of endometrial glands and stroma outside the lining of the uterine cavity.

It is estimated that between 30 and 40 per cent ofpatientswith endometriosis complain of difficulty in conceiving. In many patients there is a multifactorial pathogenesis to this subfertility.

In the severe stages of endometriosis there is commonly anatomical

distortion, with peri-adnexal adhesions and destruction

of ovarian tissue .

male subfertility

• Disorders of spermatogenesis

• Impaired sperm transport

• Ejaculatory dysfunction

• Immunological and infective factors

Male Subfertility

The main cause of male subfertility is low semen quality.

Semen quality is a measure of the ability of semen to accomplish fertilization. Thus, it is a measure of fertility in a man. It is the sperm in the semen that are of importance, and therefore semen quality involves both sperm quantity and quality.

Subfertility associated with viable, but immotile sperm may be caused by Primary Ciliary Dyskinesia.

WHO criteria for Semen Analysis

Semen Analysis

Volume 2-5 ml

Liquefaction time Within 30 minutes

Sperm Concentration 20 Million/ml

Sperm Motility >50% progressive motility

Sperm Morphology >30% normal forms

White Blood Cells <1 million/ml

Causes of male subfertility :

1- Varicocele : in 12 % of normal men and 25% of men with semen abnormalities.

- Increase scrotal Temp.

- Hypoxia .

- Raised testicular pressure.

2- Genetic causes : azoospermia is associated with karyotypicabnormalities in 15 % of cases of which 90% r 47XXY ( Klinfiltersyndrome ).

Structural abnormalities of chromosome.

Deletion of genes on the Y chromosome.

10/99

29

3- Cryptochidism:

Untreated for 2 years.

4 – 10 folds increase in the risk of testicular cancer.

4- Orchitis :

Mumps most cmn coz.

17 % of orchitis r bilateral.

It coz atrophy of seminiferous tubles.

5- Occupational & enviromental factors:

Tobacco & alcohol .

10/99

30

6- Iatrogenic :

Hormonal tx , cimetidin, colchicine chemotherapeutic agents.

7- Genital tract obstruction:

* 2% associated with cystic fibrosis.

8- Hypogonadotropic hypogonadism.

9- Coital dysfunction1- ( impotence ) : majority is psychological,2-( Hypospedis)

10- Immunological cause; ( sperms move around there selves or agglutinated ).

11- Idiopathic impairment of semen quality.

10/99

31

WHO classification of Semen Variables

Normozoospermia Normal ejaculate

Oligozoospermia Sperm concentration fewer than 20x106/ml.

Asthenozoospermia Less than the normal value for motility.

Teratozoospermia Fewer than 30% spermatozoa with normal morphology

Oligoasthenoterato-zoospermiaSignifies disturbance of all three variables.

Azoospermia No spermatozoa in the ejaculate

Aspermia No ejaculate

Unexplained infertility

Unexplained infertility is diagnosed where routine investigations

including semen analyses, tubal evaluation and tests of ovulation yield normal results. Intrinsic differences within populations and variations in investigation protocols have led to a wide range in the reported prevalence of unexplained infertility, but most clinics now report incidences of 20–30%. Failure of routine tests to detect any obvious contributory factors has led clinicians to speculate about numerous factors contributing to a diagnosis of

unexplained infertility

Contributory factors to unexplained infertility

Luteal phase deficiency

Luteinized unruptured follicle (LUF) syndrome

Hyperprolactinaemia

Occult infection

Immunological causes

Psychological factors

Management of subfertility

History

Full medical and surgical history taken from both the male and female partner:

Drug History?

Family History and Lifestyle:

Use of Alcohol, smoking, and recreational drugs?

Coital frequency or any difficulties with coitus?

Past operation?

STDs, Past or Present?

Specific History Questions for Women?

Gynecological History?

Details of Menarche, Menstrual Cycle, and Menstrual Frequency.

Women with Irregular Menstruation?

Symptoms of PCOS?

Thyroid Disorder?

Hyperprolactinaemia?

Specific History Questions for Men?

Fathered any previous pregnancies?

History of mumps or measles?

History of testicular trauma, surgery to testis?

Examination

Examination of both partners is essential to ensure normal reproductive organs.

Males:

Assess testicular size, consistency, masses, absence of vasdeferens, varicocele, evidence of surgical scars.

Small Testes:

Primary testicular failure

Female:

Full general and pelvic examination.

INVESTIGATIONS

FOR ANOVULATION

progesterone tracking.

Where the cycle length is either longer or shorter than 28 days a single day-21 progesterone level may be insufficient to pinpoint ovulation and serial progesterone checks may be needed (progesterone tracking). For example, in a 28–35 day cycle progesterone tracking could be started from day 21 and continued weekly until the next period begins.

INVESTIGATIONS

Where periods are either very irregular or absent

it may be impractical to estimate progesterone

levels. Instead, additional biochemical investigations

are indicated to establish a possible endocrine cause

of oligo/anovulation

INVESTIGATIONS

These include early follicular phase FSH and LH, prolactin, TSH, and where PCOS is suspected, serum testosterone .

Where an adrenal cause is to be excluded,

DHEA and DHEAS, 17–OH progesterone need to be checked.

FSH and LH levels should be checked in the early follicular phase(days 1–3) in order to avoid the normal Mid cycle surge which can lead to abnormally high values.

Where accurate timing of the test is impossible(as in

amenorrhoeic women), a serum sample can be obtained at

any time and the results interpreted with reference to the

following period.

Investigations

Investigation tubal factors

1-Hysterosalpingography day 10 of mc radio-opaque substance.

2-Hysterosalpingo contrast sonography .galactose solution.

3-Laparoscopy.methylene blue

INVESTIGATIONS

Uterine factors Intra-uterine adhesion (Asherman‘s

syndrome),sub mucous fibroid,uterineabnormality.

Cervical hostility

Sperm antibody . diagnosis is by post coital test

Treatment

All couples trying for a pregnancy will benefit from some

general advice such as cessation of smoking and limiting

alcohol intake. Pre-treatment counselling should include

advice about general lifestyle measures including the need

to achieve an optimum BMI. This will involve weight loss

in women with a BMI of over 30

Ovulation problems

Ovulation induction can be performed using antioestrogenmedication, including clomiphene citrate

and tamoxifen or exogenous gonadotrophin, to stimulate the development of one or more mature follicles.

Clomiphene citrate is administered during the follicular phase of the menstrual cycle. It is thought to act by increasing gonadotrophin release from the pituitary, leading to enhanced follicular recruitment and growth. It is effective at inducing ovulation in 85 per cent of women and can be used for a maximum of a year.

Clomiphene citrate

It is administerd orally for 5 days from 2nd

day of mc 50mg /d.

Side effect:

Hot flushes

Bloating

Multiple gestations

Visual changes

Ovarian hyperstimulationsyndrome(OHSS) is a potentially serious side effect of ovulation induction and is associated with large ovarian cysts. There is increased vascularpermeability leading to ascites, pleural effusions and intravascularHypovolaemia . Thrombosis may ensue. OHSS is found particularly in patients with polycystic ovarian syndrome and older women. The mild form found in approximately 30% of patients,responds to conservative management and no further ovarian stimulation . The severe form (found in < 2%)requires fluid replacement ,antithrombotic measures and bed rest.

Ovulation can also be induced with exogenous

gonadotrophins given by daily injection from the

beginning of the cycle. The dose is titrated against the

individual response and is monitored by an ultrasound

assessment of follicular number and size. Ovulation is

usually triggered with an injection of human chorionic

gonadotrophin (hCG, which binds to the LH receptor)

when 1-3 follicles are 18 mm in diameter.

Tubal disease

The treatment of tubal disease aims to restore normal anatomy, but the chance of success depends on the severity and location of the damage as well as on the

skills of the surgeon. In-vitro fertilization (IVF) is an alternative to surgery and would be recommended if there were extensire damage or intrafallopian tubal

damage, or if surgery failed to restore patency. If peritubal or peri-ovarian adhesions are present, they can be removed by a laparoscopic adhesiolysis.

When thefimbriae are also involved, a fimbrioplasty to removethefimbrial adhesions and repair the fimbrial disease can be successful. Although at least 5 per cent of the resulting conceptions will be ectopic, intrauterine pregnancy

rates of 50 per cent can be seen after 6 months

10/99

57

Bromocriptine ; for hyper prolactinemia 2.5 mg bed time.

Treatment of thyroid ,infectionAnd endometriosis.Treatmeant of cervical hostility by IUI.

FOR male patient:1-Surgical RX of varicocele&Obstructive defects.2-Retrograte ejaculation by alph sympathomimetics.3-Rx of secondary hypogonadism or

hyperprolactinemia.4-Use of donar sperm.

Management : Assisted conception

1-Gamete intrafallopian transfer(GIFT):

Extraction of the oocytes is folloed by the transfer of gametes(sperm&oocyte) into a normal fallopian tube by laparoscopy.

2-Zygote intarafallopian transfer(ZIFT):refers to the placement of the embryos into the tube via laparoscopy after oocyte retrieval and fertilization.

3-Intracytoplasmic sperm injoction( ICSI):a single spermatozoon is injected microscopically in to each oocyte, and the resulting embryos are transferred transcervically into the uterus. The advent of ICSI has revolutoinized fertility treatment for male factor.

4-In vitro fertilization(IVF):refers to controlled ovarian hyperstimulation, ultrasonographically guided aspiration of oocytes laboratory fertilization with prepared sperm, embryo culture, and transcervicaltransfer of the resulting embryos into the uterus.

Indications of IVF:1-Tubal conditions like large hydrosalpings, absence of

fimbria, sever adhesive disease, repeated ectopic pregnancies or failed recnstructive surgical therapy.

2-Endometriosis if tratmeant failed.3-Unexplained subfertility.4-Male type low sperm count and abnormal morphology.5-HIV positve males.6-Men and women seeking fertility presevation after

chemotherapy or irradiation of their pelvic regions.

Surgical

Adhesions, Endometriosis, Ovarian Cyst

Operative laparoscopy to treat disease and restore anatomy

Fibroid Uterus

Myomectomy-Hysteroscopy, laparoscopy, laparotomy, fibroid embolization

Blocked Fallopian Tubes amenable to repair

Tubal Surgery

PCOS unresponsive to medical treatment

Laparoscopic Ovarian Drilling