Polycystic Ovary Syndrome

Polycystic ovary syndrome is manifested by a wide range of clinical symptoms and endocrine and metabolic abnormalities. PCOS is defined as higher levels of androgens (male sex hormones) in combination with irregular menstrual cycle (longer cycles, missing menstrual bleeding). The certainty of PCOS diagnosis can be supported by typical morphologic symptoms of ovaries (many small ovarian cysts) found by ultrasonography; however, normal appearance of ovaries does not exclude PCOS diagnosis.

Age and Assisted Reproduction

Optimal fertile time is between the ages of 20 and 30. Age 25 seems to be optimal. Reproductive ability slowly decreases after age 30 and starts to decline rapidly around age 35. 

Just under 30% of women after age 40 and only about 10% of women in their mid-forties, give birth successfully after one or more IVF attempts.

Over 60% of all women older than 45 are infertile. 

Tubular Factor

Thickening of the fallopian tube walls, deficits in their function, narrowing or even blockage are often the result of some type of pelvic inflammation or can be caused by undiagnosed infection, such as after an abortion or by an asymptomatic infection (e.g., chlamydia or gonorrhea).

Ovulation Disorders

Symptoms can show various combinations. Ovulation problems can include anovulation (missing ovulation), oligoovulation (infrequent ovulation) and luteal phase disorders (insufficient function of the corpus luteum, which forms after ovulation on the ovaries and produces an important hormone – progesterone). Ovulation disorders can be a result of many different causes, including general body diseases.

Treatment for Endometriosis

Conservative – hormonal treatment

This treatment has a high success rate (75 – 95%), but 25 – 50% patients can experience recurrence of endometriosis. Response to treatment is individual and, to a certain extent, depends on laparoscopic and histologic findings. The conservative treatment works best for peritoneal adhesions, it is less effective for ovarian adhesions and essentially non-effective for rectovaginal endometriosis.

Medications used in hormonal treatment block the function of the hormones from the main hormonal control organ – the hypophysis. They lower the levels of the ovarian hormone estrogen, which prevents the periodic changes of the endometrium. Treated endometrial adhesions get smaller and eventually completely disappear. The treatment takes 3 – 6 months. Used medications are usually applied subcutaneously or by a simple intramuscular injection (DIPHERELINE, DECAPEPTYL, ZOLADEX). Side effects of this treatment include temporal absence of menstruation, depression, mood swings, hot flashes and sleeping disturbances; however, they only last for the duration of the treatment.

Hormonal contraception is another type of hormonal treatment. It lowers hormonal stimulation of the endometrial lining, but it is not as effective as the above mentioned treatment.

Surgical Treatment

If endometriosis is diagnosed during laparoscopy, then surgical removal of the adhesions and the cysts-endometriomas-is an important part of the treatment. Surgical reduction of the adhesions enhances the effectiveness of the hormonal treatment.

If infertility is the main problem, the treatment is individually based. Treatment then utilizes assisted reproduction methods often combined with hormonal and surgical treatment.

 
Optimal fertile time is between the ages of 20 and 30. Age 25 seems to be optimal. Reproductive ability slowly decreases after age 30 and starts to decline rapidly around age 35. 

Just under 30% of women after age 40 and only about 10% of women in their mid-forties, give birth successfully after one or more IVF attempts.

Over 60% of all women older than 45 are infertile. 

Age and Fertility | Although the direct relationship between the woman’s age and her decreasing reproductive ability is generally well known, women still postpone their first attempts to conceive to later years. Optimal fertile time is between the ages of 20 and 30. Age 25 seems to be optimal. Reproductive ability slowly decreases after age 30 and starts to decline rapidly around age 35. About 10 to 15 years prior to the onset of menopause, the decrease in the quantity of follicles in the ovaries starts to accelerate. At the same time, the blood level of the FSH hormone, which stimulates follicle growth, is increasing. These changes are reflected in the lower quality and potency of the follicles, which leads to decreased egg production. The decrease affects not only the number of eggs in the ovaries, but also their quality and suitability for conception. The menstrual cycle also demonstrates certain changes. It can remain regular, but the first phase (follicular), during which the follicle matures, shortens over time.

Also, a number various complications affecting the reproductive ability occur more frequently with age-the number of menstrual cycles with ovulation decreases; more uterine abnormalities occur (myomas, changes in blood flow, endometrial pathologies, etc.); sexual activity declines; and spontaneous miscarriages occur more frequently.

Age and Assisted Reproduction

From all the couples around 30 years of age, 7% are infertile; from all couples around 40 years of age, 33% are infertile. Over 60% of all women older than 45 are infertile. The success of IVF methods also declines with age. Just under 30% of women after age 40, and only about 10% of women in their mid-forties, give birth successfully after one or more IVF attempts. To this day there are no published studies documenting pregnancy in women 46 years of age and older; generally these women are only able to conceive by using donated eggs.

Tubular Factor

Thickening of the fallopian tube walls, deficits in their function, narrowing or even blockage are often the result of some type of pelvic inflammation or can be caused by undiagnosed infection, such as after an abortion or by an asymptomatic infection (e.g., chlamydia or gonorrhea).

Endometriosis or congenital abnormalities and defects can be the cause as well. Women with damaged fallopian tubes not only have a low chance of spontaneously conceiving, but also have a higher risk of ectopic pregnancy, in which the fertilized egg is stopped along its path to the uterine cavity, nests there, and can destroy the fallopian tube or cause it to rupture and bleed into the abdominal cavity, threatening the woman´s life.

Pelvic adhesions – also known as scar tissue, usually occur between the pelvic and abdominal structures and block the contact between the fallopian tube and the ovary. This prevents egg capture during ovulation.

Pelvic adhesions usually form as a result of an inflammatory disease in a woman´s pelvic area, such as during severe inflammation of the appendix, after abdominal surgeries or during endometriosis, but also during an undetected, insidious inflammation without serious complications.

Even though modern endoscopic methods (i.e., laparoscopy) are quite advanced, the majority of pelvic adhesions are very difficult to remove and repeated surgeries can lead to the formation of new ones. That is why infertility treatment for the occurrence of lower clearance in the fallopian tubes, their blockage or pelvic adhesions, which restrict the contact with the ovaries, include assisted reproductive methods, namely outside the body fertilization – in vitro fertilization IVF.

Ovulation Disorders

Symptoms of Ovulation Disorders

  • Amenorrhoea (missing menstruation)
  • Irregular duration of menstrual cycle
  • Obesity
  • Significant weight loss
  • Galactorrhea (spontaneous flow of milk from the breast)
  • Hirsutism (abnormal body hairiness)
  • Acne

Symptoms can show various combinations. Ovulation problems can include anovulation (missing ovulation), oligoovulation (infrequent ovulation) and luteal phase disorders (insufficient function of the corpus luteum, which forms after ovulation on the ovaries and produces an important hormone – progesterone). Ovulation disorders can be a result of many different causes, including general body diseases.

Causes of Ovulation Disorders

General body diseases:
• Thyroid gland function disorders
• Hyperprolactinemia (abnormally high levels of prolactin)

Hypothalamus disorders:
• Tumors
• Impaired hormonal control and distribution as a result of:
» stress
» weight loss
» Cushing syndrome – congenital hyperplasia of the adrenal glands
» ovary or adrenal glands tumors

Hypophysis disorders::
• Tumors
• Impaired hormonal control and distribution as a result of:
» Polycystic ovary syndrome (PCOS)
» Weight loss
» Infection

Ovary disorders:
• Malfunctions:
» Genetically caused (e.g., Turner syndrome)
» Infectious
» After surgery
» Immunologic
• Polycystic ovary syndrome (PCOS)
• Tumors

The World Health Organization (WHO) Classification System of Anovulation Disorders

The classification system developed by the World Health Organization is used to determine the type of anovulation disorder. It is based on three parameters:

  • Secreted prolactin level
  • Gonadotropins (LH and FSH) level
  • Estrogen level.
GroupDiagnosisDescription
I Hypothalamic – hypophyseal failure Menstrual cycle does not exist, estrogen secretion not proven, prolactin levels not increased, low level of FSH (hypogonadotropic hypogonadism), no organic disorder in hypothalamo – hypophysis area can be found.
II Hypothalamic – hypophyseal dysfunction Many different menstrual cycle defects (luteal phase insufficiency, anovulating cycles, anovulating syndrome of polycystic ovaries, amenorrhoea), normal levels of prolactin and FSH, and detectable levels of estrogen.
III Ovary failure No menstruation, no signs of ovary functions, higher levels of FSH, prolactin level not increased.
IV Congenital or an acquired genital organ disorders No menstruation, no bleeding response to estrogen withdrawal after repeated estrogen treatments.
V Infertile women with hyperprolactinemia and manifest tumorous or inflammation – inducing processes in the hypothalamo – hypophyseal area Multiple menstrual cycle defects (luteal phase insufficiency, anovulating cycles, amenorrhoea) with higher prolactin levels and diagnosed organic disorder in the hypothalamo – hypophyseal area.
VI Infertile women with hyperprolactinemia without manifest tumorous or inflammation-inducing processes in hypothalamo – hypophyseal area Same as group V, but without diagnosed organic disorder.
VII Non-menstruating women without higher prolactine levels and without manifest tumorous or inflammation – inducing processes of the hypothalamus or the hypophysis Low estrogen production, low or normal levels of prolactin and FSH.

According to the WHO classification, about 97% of non-ovulating patients belong to group II and the remaining ones to group I. These two groups also represent patients who will most likely benefit from gonadotropine treatment to restore ovulation. Classification systems, like this one from the WHO, ensure that optimal treatment will be given to every patient. This system also allows a comparison of results from clinical and pharmaceutical intervention trials across clinical centers, and even across different countries around the world because it precisely defines (i.e., standardizes) the individual diagnostic groups. It is important to realize that although the classification systems provide useful guidelines for treatment, an individual treatment will be chosen by your doctor, taking into consideration your anamnesis, physical examination and laboratory test results.

Endometriosis

Endometriosis is a disease in which some parts of the endometrium can be found outside the uterine cavity. Symptoms include painful menstrual bleeding, prolonged pain in the lower abdomen, painful sexual intercourse and fertility problems. Endometriosis is the most frequent gynecological disorder during a female reproductive age. It is seen in 20 – 50% of infertile women and in 50% of women with pelvic pain.

The cause of endometriosis

The cause of endometriosis has yet to be determined. Several factors usually contribute to the formation of endometriosis – genetic, immunologic and hormonal. Under normal circumstances, hormonally changed endometrium flushes out from the uterine cavity during menstrual bleeding. Small parts of the endometrium are then passed through the fallopian tubes to the abdominal cavity. One of the theories assessing the formation of endometriosis suggests that the same hormonal process that takes place in the endometrium also occurs to the nested (implanted) parts of the endometrium in the abdominal cavity and pelvis.

Another theory presumes that some cells in the abdominal cavity change into cells resembling endometrium after repeated inflammations in the woman´s small pelvis or as a reaction to the higher blood estrogen levels (female sex hormones).

One of the other theories – immunologic – suggests the presence of endometrial antibodies in a female body or lower cell immunity. As a result, the woman’s immunity system does not react to the endometrial bearings, does not destroy them and facilitates nesting (implantation) of the endometrium or its transition into a different cell structure (metaplasia).

Endometriosis causes infertility by creating adhesions in the woman´s pelvic area. The adhesions restrict contact between the internal reproductive organs and cause changes in the hormonal, immunologic and biochemical processes responsible for merging of embryonic cells, early embryonic development and the transport of an embryo into the uterine cavity.

According to the location there are 4 basic types of endometriosis:

Peritoneal endometriosis – ectopic tissue in the pelvis
Colored stains several millimeters in size are usually found on the perineum during laparoscopy. Color of the stains differs based on the stage of development of the endometrial lining. Initially, they are red in color and go through the same hormonal development as the uterine lining. This leads to a local inflammation in the area of the polyps, which close themselves as the time passes. In the closed polyps, the secreted tissue is accumulated, which makes them larger and changes its color to blue. Vascular supply in the polyps gradually disappears and they transform into scars. This leads to the final stage – white endometriosis. The scarring process in the area near the fibroids can sometimes form round defects (openings) on the peritoneum.

Ovarian endometriosis – fibroids on the ovaries
This type is characterized by colored fibroids on the surface of the ovaries, which can nest themselves deep down in the ovary and form a cyst up to a few centimeters in size. The cyst is known as endometrium or an endometrial cyst. It contains brownish liquid, which is why it is often referred to as a chocolate cyst.

Endometriosis of the rectovaginal septum – endometriosis at the thin structure separating the vagina and the rectum
The presence of tough nodules is typical for this type of endometriosis. Nodules are formed by excessive production of smooth muscle fibers and ligaments in the area near the endometrial glands. This type is also frequently referred to as deep endometriosis because it affects not only the above mentioned septum, but also the ligaments between the uterus and the pelvic bones. Nodules can also form in the muscles of the pelvic organs. This endometriosis is only minimally affected by changes during menstrual cycle and it is manifested by a significant and prolonged pain.

Adenomyosis – adhesions inside the uterine muscles
This type usually does not occur as an isolated manifestation. Often, it is combined with peritoneal endometriosis, often uterine myomas – muscular nodules on the uterus. Symptoms include increased bleeding, enlarged and painful uterus and some additional symptoms typical for endometriosis, such as painful menstruation, pelvic pain and pain during a sexual intercourse.

Diagnosis of endometriosis can be determined based on the analysis of the patient’s subjective problems or by clinical examination combined with ultrasound imaging. However, the diagnosis is most often determined only after laparoscopy.

Polycystic Ovary Syndrome (PCOS)

Polycystic ovary syndrome is manifested by a wide range of clinical symptoms and endocrine and metabolic abnormalities. PCOS is defined as higher levels of androgens (male sex hormones) in combination with irregular menstrual cycle (longer cycles, missing menstrual bleeding). The certainty of PCOS diagnosis can be supported by typical morphologic symptoms of ovaries (many small ovarian cysts) found by ultrasonography; however, normal appearance of ovaries does not exclude PCOS diagnosis.

This syndrome occurs in about 5 – 10% of all women. It is important to not confuse PCOS syndrome with the condition of normal polycystic ovaries (PCO), which is a normal condition without hormonal swings diagnosed using ultrasound examination in up to 30% of women of reproductive age. The finding of PCOS alone without other fulfilled criteria does not mean a clinical PCOS diagnosis.

The cause is yet to be determined. The main factor includes lower sensitivity of body cells to insulin, which then leads to an increase in androgen production via complex chemical processes. Genetic and some other factors also contribute to PCOS.

Symptoms (usually occur individually or in small groups)

  • Irregular or missing menstruation
  • Missing ovulation (releasing of the egg from the ovary)
  • Obesity
  • Hirsutism (excessive hairiness)
  • Resistance to insulin
  • Acne
  • Numerous small cysts on ovaries
  • Enlarged ovaries – up to three times bigger than normal size
  • Infertility – inability to become pregnant after more than 12 months of unprotected sexual intercourse
  • Chronic pelvic pain – more than 6 months
  • Dyslipidemia – abnormalities of lipid levels in blood
  • High blood pressure – more than 140/90

Diagnostic Criteria

  • a chronic pattern of missed ovulation or menstrual cycle disorders (menstrual bleeding occurs late or not at all) followed by higher androgen levels after excluding other possibilities of increased androgen levels
  • supportive criteria: ultrasound finding of polycystic ovaries, the ratio of Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels ratio – LH at least two times greater than FSH

Diagnosis is based on physical examination, presence of the above mentioned symptoms, ultrasound examination and endocrine examination.

Treatment

Medications and surgical procedures are both used.

  • Weight reduction – Higher weight is associated with a more frequent occurrence of sterility and menstrual cycle disorders. Weight reduction also helps increase cell sensitivity to insulin.
  • Hormonal treatment – Taking medications that decrease androgen levels or their effect on the tissue (antiandrogens or androgen antagonists). Cyproteronacetate is the most frequently used medication. It is used, for example, in a form of a contraceptive pill (DIANE 35, MINERVA, CHLOE) or as ANDROCUR preparation. Some other medications can be applied with a great antiandrogen effect – for example, spironolakton (VEROSPIRON), flutamid (ANDRAXAN) or finasterid (PROSCAR, PENESTER).
  • Insulin sensitizers – Preparations that enhance tissue sensitivity to insulin – metformin/METFORMIN, GLUKOPHAGE, SIOFORF
  • Ovulation induction – Can be combined with additional assisted reproduction methods
  • Surgical treatment – Thin layer on the surface of the ovaries is very lightly laparoscopically drilled (ovarian drilling), which improves their ovulation functions and hormone production.
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