Introduction

to Infertility

Division of Reproductive Endocrinology Department of Obstetrics and Gynecology Gadjah Mada University

Introduction
The inability to create a desired pregnancy that culminates in the birth of a child is likely to create a life crisis for women and their partners. Women seeking fertility treatment looking for care, counsel and health teaching. Infertility is more common in older women. Moreover, increased age reduces the efficacy of treatment.
2008, March of Dimes Foundation

Infertilty
Infertility is inability of a couple to conceive after one year of sexual intercourse without contraception
Primary infertility: The inability to conceive

after 1 year of unprotected intercourse for a woman younger than 35, or after 6 months of unprotected intercourse for a woman 35 or older (Speroff & Fritz, 2005). Secondary infertility: The inability of a woman to conceive who previously was able to do so (Speroff & Fritz, 2005).

Causes of Infertility
Couples

(Speroff & Fritz, 2005)

2008, March of Dimes Foundation

Causes of Infertility
Women

2008, March of Dimes Foundation

(Speroff & Fritz, 2005)

INCIDENCE AND TREAMENT

The overall incidence of infertility has remained relatively unchanged over the past 3 years. However, the evaluation and treatment of infertility has changed dramatically during that time.

THREE MAJOR DEVELOPMENT

1. 2. 3.

The introduction of IVF (Invitro Fertilization) and other ARTs. Changes in population demographic The advances in ART and concerns about the age-related decline in fertility

Consequently, infertile couples are now more likely to seek medical advice, evaluation andtreatment.

Which Investigations!!

There is a very long list of investigations for the diagnosis of infertility, unfortunately there is no consensus on which tests are essential before reaching the exact diagnosis

Infertility investigation

Semen analysis Tubal patency by hysterography or laparoscopy Mid luteal progesterone for the diagnosis of ovulation Ultrasound Postcoital test Antisperm antibodies assays Endometrial dating Varicocele assessment Chlamydial testing Hysteroscopy Hydrolaparoscopy

Basically there are 4 factors required for getting pregnant :

Sperm

Ovum
Conception

Implantation

Investigations of infertility

Sperm transport to the side of fertilization

OOCYTE

BLASTO CYST

OVULATION - FERTILIZATION TRANSPORTATION DEVISION

When should woman go to see a doctor?

Women in their 30s who've been trying to become pregnant for six months should speak to their doctors as soon as possible. Women with the following issues should speak to their doctors:

irregular periods or no menstrual periods very painful periods Endometriosis pelvic inflammatory disease more than one miscarriage

What Increases the Risks?

Age Stress Poor diet Smoking Alcohol STDs Overweight Underweight Caffeine intake Too much exercise

Many of the risk factors for both male and female infertility are the same, they include:

Age. After about age 32, a woman's fertility potential gradually declines. Infertility in older women may be due to :

A higher rate of chromosomal abnormalities that occur in the eggs. Older women are also more likely to have health problems that may interfere with fertility. The risk of miscarriage also increases with a woman's age.

Tobacco smoking. Men and women who smoke tobacco may reduce their chances of becoming pregnant and reduce the possible benefit of fertility treatment. Miscarriages are more frequent in women who smoke. Alcohol use. For women, there's no safe level of alcohol use during conception or pregnancy. Being overweight. Among American women, infertility often is due to a sedentary lifestyle and being overweight.

Being underweight. Women at risk include those with :

eating disorders, such as anorexia nervosa or bulimia women following a very low-calorie or restrictive diet. Strict vegetarians also may experience infertility problems due to a lack of important nutrients such as vitamin B-12, zinc, iron and folic acid.

Too much exercise.

In some studies, exercising more than seven hours a week has been associated with ovulation problems. Strenuous exercise may also affect success of in vitro fertilization. On the other hand, not enough exercise can contribute to obesity, which also increases infertility.

 Caffeine
Studies

intake.

are mixed on whether drinking too much caffeine may be associated with decreased fertility. Some studies have shown a decrease in fertility with increased caffeine use while others have not shown adverse effects. If there are effects, it's likely that caffeine has a greater impact on a woman's fertility than on a man's. High caffeine intake does appear to increase the risk of miscarriage.

The Age Factor

A woman's fertility naturally starts to decline in her late 20's. After age 35 a woman's fertility decreases rapidly. A woman is born with all the eggs she'll have, and with time, the supply diminishes.

PHYSIOLOGY OF REPRODUCTIVE AGING During fetal life, germ cells rapidly proliferate by mitosis
AGE
16-20 WEEKS GESTATION AT BIRTH PUBERTY READY TO DEVELOP

GERM CELLS
6.000.000 7.000.000 1.000.000 - 2.000.000 300.000 500.000 400 500 oocytes will

(Over the next 35-40 years of

reproductive life) 37 YEARS

ovulate, the rest are lost

through atresia. 25.000

Menopause

1.000

MENSTRUAL CHARACTERISTIC
Menstrual characteristics in older women correlate with number of follicles remaining. The ovaries of regularly menstruating contain 10-fold more follicles than those of peri-menopusal women having irregular and infrequent menses. Follicles are virtually absent in the ovaries of postmenopausal women.

Time required for conception in couples who will attain pregnancy

Time of exposure 3 months % Pregnant 57%

6 months
1 year 2 years

72%
85% 93%

Common Causes of Infertility

Severe endometriosis Pelvic Inflammatory Disease (PID) Ovulation disorders Elevated prolactin Polycystic ovary syndrome (PCOS) Early menopause Benign uterine fibroids Pelvic adhesions

Endometriosis

Occurs when the uterine tissue implants and grows outside of the uterus, affecting the function of the ovaries, uterus and fallopian tubes. Scar tissue can block the fallopian tubes and prevent the egg from entering the uterus. There is a 25-35% rate of infertility in moderate to severe cases of Endometriosis

The incidence of infertility attributable to endometriosis is difficult to assess.

It is estimated that between 30% and 50% of women with endometriosis have some degree of infertility

Severe disease may distort pelvic anatomy

Impaired egg release
Distortion of the fallopian tubes

Inhibited ovum pick up

The most common places for implantation are:

the ovaries, fallopian tubes, bladder and intestines, uterine wall, and the lining of the pelvis. In very rare cases it may be found in the lungs, surgical wounds (cesarean section scars), brain tissue and the vaginal wall. Adhesions (scar tissue) can block the fallopian tubes and prevent the egg from entering the uterus. There is a 25-35% rate of infertility in moderate to severe cases of Endometriosis, resulting primarily from damage incurred to the ovaries and fallopian tubes.

Can Endometriosis cause infertility ?

Pelvic Inflammatory Disease

Pelvic inflammatory disease (PID) is a spectrum of infections of the female genital tract that includes endometritis, salpingitis, tuboovarian abscess, and peritonitis.

Infection of the uterus (womb), fallopian tubes and other reproductive organs is a common and serious complication of some sexually transmitted diseases (STDs), especially chlamydia and gonorrhea. PID can damage the fallopian tubes and tissues in and near the uterus and ovaries. Untreated PID can lead to serious consequences including infertility, ectopic pregnancy, abscess formation, and chronic pelvic pain.

Pelvic Adhesions

Pelvic adhesions are bands of scar tissue that bind organs after pelvic infection, appendicitis, or abdominal or pelvic surgery This scar tissue formation may impair fertility.

UTERINE FIBROID

Fibroids are benign tumors in the wall of the uterus May cause infertility by blocking the fallopian tubes

Ovarian failure/ovarian dysfunction :

Ovarian failure can be a consequence of medical treatments, or the complete failure of the ovaries to develop (Turner's Syndrome). Ovarian failure can also occur as a result of treatments such as chemotherapy and pelvic radiotherapy for cancers in other body areas. These therapies destroy eggs in the ovary.

Guidelines of infertile investigations

1.

2.

3.

Investigation of infertility in the female should not be commenced until the male has been evaluated. There should be discussion with both parters so that the outline of the investigation is understood. Sexuality patterns of the couples should be discussed as it is quite surprising at times how little an infertile couple know about this subject.

1. Male investigations
conventional semen analysis A variety of sperm function tests such as in vitro mucous penetration test, hamster egg penetration test and post coital test.

2. Assessment of ovulation
Basal body temperature Mid luteal serum progesterone Endometrial biopsy Ultrasound monitoring of ovulation.

3. Tubal factor (Possibility of conception)

Hysterosalpingography (HSG) Laparoscopy Falloscopy Hysterosonography Hydrolaparoscopy.

Other more specific inverstigations :

The peritoneal factors are assessed by laparoscopy The uterine factor by hysterosalpingography and hysteroscopy. Immunological factors are evaluated by a variety of special tests.

Hysteroscopy (HSC)

HSC is not a routine investigation of infertile couples as there is no evidence linking treatment of uterine abnormalities with enhanced fertility. (RCOG,1999)

1. Take Care
Care must be taken to avoid exploitation of the infertile couple with expensive unnecessary tests
( ESHRE Capri Workshop 1996)

2. Concept to keep in mind

A simplified approach will lead to a significant reduction in both the time and cost of investigating an infertile couple. (Strandell 2000)

Collection of semen sample

by masturbation Temp (15C to 38C) deliver quickly Husband should not have sexual intercourse 3 to 4 days before essesment. Note : As many as 25% of proven fertile men have sperm concentration below 20 million/ml

Hysterosalpingography (HSG)

Although HSG is of low sensitivity, its high specificity, makes it a useful screening test for ruling in tubal obstruction. In case of abnormal finding, diagnostic laparoscopy with dye transit is the procedure of choice (Swart et al, 1995) HSG is cheaper Performed as an outpatient procedure Although often painful has a low incidence of complications ( RCOG, 1999 )

Advantages

Conception after HSG

HSG has a low prognostic value, the outcome of normal HSG adds little to predicting the occurrence of pregnancy. Supprisingly, after a normal HSG 40% become pregnant (Mackey, 1979). However, when HSG shows bilateral obstruction, the chance of getting pregnant is only minimal.
(Maas et al, 1997)

Precaution

Before uterine instrumentation (as HSG or HSC) appropriate antibiotic prophylaxis against chlamydia should be given ( RCOG,1999 )

Summary
From the above data, it seems that serum progesterone for detection of ovulation, hysterosalpinghography for tubal patency and semen analysis are the basic essential tests for diagnosis of infertility. Other tests may have a role in special situations or as a part clinical trials. Laparoscopy should be reserved as a further diagnostic procedure or in combination with endoscopic surgery