In Vitro (IVF) Evaluation of the Female

Infertility is seen in approximately 10-15% of all couples. During the evaluation of infertility both partners shoud be examined.

The evaluation has three steps: a detailed history, physical examination and labarotory tests.

• Detailing the couple’s history is the first step towards identifiying the possible reason or reasons for infertility. The women’s age, the duration of infertility, past treatements or operations, past diagnostic tests, menstrual characteristics, pain during periods or sexual intercourse, past obstetric history, current medical ilnesses or medications, allergies, family history, smoking or alcohol consumption are evaluated.
• Next is a physical examination incluiding weight, height, examination for signs of thyroid problems or androgen excess and vaginal and cervical examination.
• The third step is to determine which laboratory tests needed.

The most common identifiable female factors

• Ovulatory dysfunction
• Maternal age
• Tubal abnormalities
• Uterine problems

Ovulatory Dysfunction
Ovarian Reserve Testing
In normal circumstances, an immature follicle containing an egg develops and ovulates. Irregular or abnormal ovulation may lead to infertility. Anovulation, the absence of ovulation, is the most common cause of irregular menses (periods). In patients with diminished ovarian reserve, poor response to drugs, early rupture of the follicles, no egg in pick up and poor IVF outcomes occur more frequently than the patients with normal ovarian reserve.

The accurate evaluation of ovarian function and reserve (the number of eggs capable of being matured that are still remaining in the overy) is important for choosing the best strategy when planning fertility treatment. There are several ways to evaluate them, including a detailed history, ultrasonographic evaluation and biochemichal evaluation.

Menstrual History
Menstrual history is important. Regular menses almost always indicate that ovulation is normal whereas irregular periods usually together with excessive hair growth. High levels of serum androgens may indicate polycystic ovary syndrome furthermore, irregular menses may indicate diminished ovarian reserve and the latter can be distinguished from polycystic ovary syndrome by the evaluation of Anti-Müllerian Hormone.

Ultrasonographic evaluation
The ovarian volume and egg count can be measured using ultrasonography.Small follicles containing eggs (antral follicles) are counted.Antral follicles are small follicles (2-8 mm in size) that are visible on the ovaries via ultrasonography.Accordingly, the ovarian reserve is classified as diminished or low (four or fewer eggs), normal (five to ten eggs) or hyper responder (more than ten eggs). Also ovarian volume is important, severely diminished ovarian volume is usually together with diminished ovarian reserve.

Biochemical Evaluation
Among the most helpful tests are those which determine the basal antral follicle count, and the levels of basal follicle stimulating hormone (FSH) and Anti-Müllerian hormone (AMH).

A FSH value lower than 10 IU/l is normal, whereas a level above 20 IU/l indicates a very diminished reserve. In order to start an IVF-ICSI treatement, it is desirable for FSH is to be lower than 15IU/ml. Above this, poor IVF results such as no response to medications, fertilization failures or embryo arrest are common. FSH levels measured on the third day of the period are important.

The E2 level, also measured on the third day of the period, is not a basic test but gives additional information. An E2 lower than 80 pg/ml is normal on day 3, whereas early elevation of E2 (over 80 pg/ml) may indicate a diminished reserve or there may be an ovarian cycts which could be detected by USG.

AMH is often used to evaluate the reserve, AMH is secreted from the ovarian follicles and therefore reflects the ovarian egg pool. An AMH level below 1 ng/ml is considered low, between 1 and 3 – considered normal, whereas the values over 5 ng/ml indicate to a high response.

Individualising treatments according to ovulatory dysfunction
Treatment protocols and stimulatory drug doses are individualized for each patient.

Patients with diminished ovarian reserve:
High doses of stimulatory drugs may not increase the number of eggs, so it is better to use the minimum dose to stimulate the ovaries, thereby improving egg quality.

High responder patients and Polycyctic ovarian (PCO) patients:

If the ovarian reserve is high, it is important to select the minimal dose in order to prevent ovarian hyperstimulation, a condition which can lead to fluid gathering in the peritoneal and pulmonary cavities. PCO patients also have an increased risk of hyperstimulation.

Maternal age
Fertility declines with advancing age, especially after the mid-30s. After the age of 38 in addition to low ovarian reserve, there is a continual increase in the rate of chromosomal abnormalities in the eggs (aneuploidy). Aneuploidy in embryos lowers the implantation potential and increases the abortion risk. We advise older women not to delay treatment if their hormonal tests and ultrasonographic findings are suitable. After the age of forty, even months are important, as, especially after the age of 43, the success rate dramatically decreases. We do not offer IVF to female patients after the age of 45.

If the patient’s hormonal status and ultrasonographic findings are suitable, ART can be started. However, especially after 43years, success rate dramatically decreases. We do not offer IVF after 45 years.

Pregnancy ratio for a woman over 40 is also decreased. Furthermore, we must also take into consideration that the risk of chromosomal anomalities and miscarriages increase with advanced maternal age .

Tubal abnormalities
Fallopian Tubes
For fertilization to take place, sperms must pass through the cervix and uterus, and reach the ovum by passing through the fallopian tubes. 30 to 40 % of the causes of infertility relate to abnormal tubal functiom, so it is important to check whether the tubes are open or not, and whether they function normally or not. Past abdominal operations, pelvic infections and endometriosis can damage tubes.

A hysterosalpingogram (HSG test) can show obstructions and adhesions in the tubas. If any abnormalities are observed, the next step may be a laparoscopy. Although a laparoscopy may help to correct the peritubal adhesions, severely damaged tubes cannot be corrected and in these cases IVF is the best treatement.

Swelling of the tubes (hydrosalpinxes) can also prevent successful pregnancy. Fluid accumulating in the tubes may flow back to the uterus, preventing implantation or increasing the risk of abortion and ectopic pregnancy.

Problems originating from the uterus
Some congenital uterine malformations, myomas, polyps and adhesions due to some infections or previous intrauterine operations may impair the implantation of the embrio.

Congenital malformations affect pregnacy outcome rather than infetility. There may be an increased risk of miscarriage or preterm labor.

Polyps are benign growths that can occur in the uterine cavity and that feed on oestrogen. They range in size from a few millimeters to several centimeters and can be asymptomatic. If the polyps measure over 1.5 cm they can have a negative effect on implantation and should be removed by hysteroscopy prior to IVF.

Myomas (leiomyomas or uterine fibroids), are benign tumors that can grow in the uterus. Most often, they are located on the outside surface (subserosal) or within the muscular wall of the uterus (intramural). In these instances, the fibroids may not interfere with conception. However, if they are situated in the inner side of uterus (submucosal) or are placing pressure on the cavity, they should be removed by surgery.

Procedures that may be needed before or during treatment

• Hysterosalpingography (HSG)
• Hysteroscopy
• Laparoscopy

What is a hysterosalpingography (HSG)? Why and when is it performed?

A hysterosalpingography (HSG) is a radiographic evaluation of the uterine cavity and fallopian tubes after the injection of a radio-opaque medium through the cervical canal. HSG is performed two to five days after the end of the period. You may feel little pain during the passage of the medium through the tubes.

HSG may be helpful if there is a history of pelvic infection, abdominal surgery, endometriosis or appendix inflammation, which could indicate the possibility of tubal damage. In cases of repeated IVF-ICSI failure it is essential to see the fallopian tubes and rule out any fluid collection.

During HSG, the pressure of the radio-opaque agent can sometimes clear tubes that have become blocked by mucus. If this happens, there is a possibility of a spontaneous pregnancy following HSG.

Hysteroscopy or laparoscopy may be needed for confirmation of the diagnosis of any abnormality found in HSG, of for the treatment of such a diagnosis.

What is a hysteroscopy? Why and when is it performed?
This technique allows us to view the uterine cavity with an optic camera. Endometrial polyps, adhesions in the cavity, myomas close to the cavity and uterine cavity abnormalities may be diagnosed and treated. A hysteroscopy is performed two to five days after the end of the period.

What is a laparoscopy? Why and when is it performed?
This is the final diagnostic procedure in the investigation of a infertile couple. It is just the examination of the abdominal cavity with a minor abdominal surgery. It can be carried out using a laparoscope, a flexible fiber optic instrument, which is passed through a small incision in the abdominal wall. It is performed two to five days after the end of the period.

Procedures which can be carried out by laparoscopy include the treatment of ovarian cysts, tubal pathologies or ectopic pregnancies, the lysis of adhesions, and the excision of myomas. Both diagnosis and treatment can be carried out during a laparoscopy.

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