Polycystic Ovary

It is the most common endocrine disorder in women of reproductive age and is one of the leading diseases leading to infertility due to ovulation problems. It was first discovered and diagnosed by Stein Leventhal in 1935.

According to the data of the World Health Organisation, PCOS is seen in 8-13% of women of reproductive age, but 70% of the affected patients in the world are not diagnosed. Menstrual irregularities can be observed in women in the first 2-3 years of puberty. In this period, PCOS should not be diagnosed only because of menstrual irregularities.

The cause of PCOS is not known exactly. It is a congenital and lifelong disease. PCOS, in which some genetic and environmental factors are also held responsible for its formation, is a disease that can be seen in women of reproductive age and can cause long-term problems. There is a familial predisposition, if one of the family members has it, it is highly likely to be seen in others.

PCOS can also cause biological and psychological disorders related to obesity, body image and infertility. PCOS patients are at risk for heart disease, high blood pressure, diabetes, high cholesterol and cancer.

Different combinations of clinical conditions such as increased hair growth (on arms and legs, abdomen, back and face), acne, hair loss, ovulation disorder (anovulation) are observed in PCOS patients. These findings due to hormone dysfunction are exacerbated by weight gain. Over the years, it may cause depression, mood changes, diabetes, heart diseases, high cholesterol, high blood pressure and uterine cancer.

For diagnosis and treatment, it is necessary to consult a specialist doctor who has experience in this field and follows current information.

Normally, women menstruate regularly every month (every 21-35 days). Women may experience menstrual irregularities within 1 year after their first menstruation. However, menstrual irregularities seen after 1 year should be investigated for PCOS. Since PCOS patients have ovulation problems, menstrual periods may be uncertain.

Menstrual irregularities may occur for the first 1 year after the first menstruation. Within 1-3 years, the first menstrual cycle should be between 21-45 days.

• Starting 3 years after the first menstruation and until the premenopause period, the menstrual cycle should be between 21-35 days (or more than 8 menstrual cycles per year).
• 1 year after the first period, it is not normal for any menstrual cycle to last more than 90 days.
• Until the age of 15 years or 3 years after breast development (telarche), no menstrual cycle is not normal.

It is more difficult to diagnose PCOS in adolescents. It is recommended that adolescents should be re-evaluated 8 years after their first period.

The cause of PCOS is not clear. Genetic and environmental causes may be responsible, as well as insulin resistance hormone imbalance is also responsible for the formation of PCOS.

If a person's mother or sisters have PCOS, the risk of PCOS increases. However, it is not certain that it is hereditary.

In PCOS disease, ovarian androgen production is increased. Androgens are normally known as male hormones. Testosterone, the male hormone, is produced more than normal. Ovulation problems occur due to changes in the secretion of LH and FSH hormones from the hypothalamus and pituitary glands in the brain. Eggs cannot fully mature and hatch.

In PCOS, androgen production and androgen level in the blood increase due to increased insulin resistance and insulin level. Insulin is the hormone that regulates sugar (glucose) in the body.

In PCOS patients planning pregnancy, weight, blood pressure, smoking, alcohol, diet and nutritional status, folate supplementation (higher dose in those with BMI>30), exercise, sleep and mental, emotional and sexual health should be considered and optimised to improve reproductive and pregnancy outcomes and overall health. Underlying health problems should be treated and patients stabilised.

Pregnant women with PCOS have a high-risk pregnancy.

There is an increased risk of excess weight gain, miscarriage, gestational diabetes, gestational hypertension and pre-eclampsia, developmental delay in the baby, low birth weight, preterm birth and caesarean section. However, these risks do not increase in the case of IVF pregnancy.

Since it will be in the risky pregnancy category, PCOS patients planning pregnancy should be examined in detail. Blood pressure control and weight measurement should be performed, and 75 g sugar loading (75 g OGTT) should be performed in addition to routine blood tests. If 75 g OGTT was not performed before pregnancy, it should be performed at the beginning of pregnancy and between 24-28 weeks.

Weight gain and preterm labour can be prevented by continuation of metformin in pregnant women who have been started on metformin, but gestational diabetes, late miscarriages and hypertension cannot be prevented. The long-term consequences of metformin exposure on child health are uncertain.

Miscarriage rate increased and live birth rate decreased in overweight pregnant women. Therefore, it is important to lose weight before pregnancy.

In the general population, up to 15% of couples who have regular intercourse cannot get pregnant within the first 1 year. This condition is called infertility. Although there are many causes of infertility, the most common cause of infertility caused by ovulation problems is polycystic ovary syndrome (PCOS).

PCOS is the most common cause of androgen excess and ovulation problems (oligo-anovulation) in women of reproductive age. The incidence of infertility in PCOS patients is approximately 70%. However, it is possible to treat infertility in PCOS patients and women with PCOS can become pregnant and give birth to children with treatment. Therefore, PCOS patients who cannot conceive are recommended to consult an infertility specialist.

The long-term problems of PCOS patients should be explained in detail together with the treatment of infertility and patients should be informed about how to take precautions.

The risk of uterine cancer is increased in PCOS patients who do not menstruate for a long time, have thickened uterus, have Type 2 diabetes and are obese.

It is recommended to take a uterine biopsy from PCOS patients with uterine thickening.

• Irregular menstrual cycle (no menstruation, 9 or less menstruation in a year, changes in the amount of menstrual bleeding)
• Infertility, inability to conceive due to ovulation problems
• Excessive weight gain; fat accumulation, especially around the waist
• Increased hair growth (especially on the waist-back, face, abdomen, chest)
• Thickening of the arms and legs
• Increased adiposity (back, face, chest)
• Acne breakouts
• Hair loss
• Difficulty in weight loss
• Anxiety and depressed mood
• High blood pressure
• Insulin resistance and risk of diabetes in the future
• Thickening of the uterus and risk of uterine cancer in the future
• High cholesterol
• Snoring and sleep apnoea
• Depression, anxiety problems.

Although not seen in every PCOS patient, the problems that PCOS disease may cause are listed below;

• Infertility
• Fatty liver disease, high cholesterol
• Hypertension
• Depression
• Diabetes
• Womb cancer
• Sleep apnoea

Young women who are diagnosed with PCOS stress themselves with the thought that they will not have children. However, it should be known that PCOS does not cause infertility in every woman. PCOS can cause infertility at a rate of 60-70%. Pregnancy can be possible by using assisted reproductive techniques in PCOS patients who complain of infertility.

In polycystic ovary disease, insulin elevation and insulin resistance, excess LH hormone, FSH hormone deficiency, and androgen excess can be seen and this can affect egg quality and cause implantation failure and miscarriage.

Follicles fail to develop and mature and ovulation, i.e. the release of the egg from the ovary, cannot occur.

The number and quality of eggs decrease with age. After 35 years of age, the fertility (fertility) of the woman decreases. Some studies have reported that the age-related decrease in fertility is slower in PCOS patients. After the age of 40, PCOS symptoms also decrease.

The highest chance of natural pregnancy in PCOS patients with regular ovulation and no additional diseases that may cause infertility is before the age of 35. PCOS patients whose body mass index, metabolic and hormone values are under control have a high chance of becoming pregnant within one year.

PCOS is associated with menstrual irregularities and anovulation (ovulation problems) and therefore reduced fertility.

PCOS patients have a very good egg reserve. They are good candidates for egg freezing as a large number of eggs will be produced in egg stimulation treatments.

In vitro fertilisation is the most common treatment method used by PCOS patients to get pregnant. The chance of success in IVF treatment is around 70%. Of course, this success chance varies depending on age. However, the live birth rate of PCOS patients over 35 years of age is higher than non-PCOS patients of the same age.

In PCOS patients with ovulation problems, some drugs such as clomiphene citrate or letrazole can be used to help ovulation and improve egg quality. In some countries, they are available for off-label use. Although they are successful treatments, especially the safety of letrazole treatment has not yet been proven.

1. Should take an anti-inflammatory diet that can be adapted to their lifestyle
2. Avoid stress
3. Should not smoke and consume alcohol
4. lose weight or keep fit through exercise
5. Insulin resistance should be corrected
6. Menstruation should be regulated
7. The presence of ovulation should be monitored with some tests
8. May receive supportive therapy; Inositol, anti-oxidant therapies (not yet proven)

Since there is no definite information, it is not yet possible to make a clear comment.

No, not always. It would be healthier to look at the level of progesterone in the blood to determine whether ovulation has occurred.

It is a hormone that shows ovarian reserve. It tends to decrease with age. It peaks between the ages of 20-25. It tends to be lower in those with high body mass index. It can be measured at every stage of the menstrual cycle.

According to many studies, AMH value may be lower than normal in women using oral contraceptives (birth control drugs). However, this effect is reversible.

PCOS can be diagnosed with clinical and laboratory findings. Monitoring a single finding is not sufficient for diagnosis. There is no single test that makes the diagnosis of PCOS.

In adults, PCOS can be diagnosed if two of the following 3 items are present (Modified Rotterdam Criteria);

1. Anovulation, i.e. menstrual irregularity due to ovulation disorder (such as 9 or less menstruation per year) or elevated AMH (Antimullerian Hormone) in the blood.
2. Polycystic appearance on ultrasound. (There should be at least 20 cysts (follicles, sacs) of 2-9 mm in each ovary seen on transvaginal ultrasound, and at least 10 follicles should be observed in each ovary on transabdominal ultrasound)
3. Increased hair growth, acne, oily skin, hair loss, hair loss, fat around the navel due to high male hormone called testosterone in the blood or detection of high testosterone hormone in the blood.

If a combination of two of these findings is observed, PCOS can be diagnosed. In adolescents (between the ages of 10-19), anovulation (menstrual irregularity) and high male hormone (androgen) levels should both be present in the diagnosis. There is no need for ultrasound or AMH in the blood.
Other diseases should be excluded before making a diagnosis. In particular, hormones such as TSH, T4, prolactin and 17 hydroxyprogesterone should be examined in the blood to exclude thyroid disease, high prolactin and adrenal hyperplasia. In more serious cases such as absence of menstruation for at least 6 months, Hypogonodotropic Hypogonadism, Cushing's Disease and adrogen hormone producing tumours should be excluded. Total testosterone and free testosterone, DHEAS and sometimes Androstenedione should be analysed in the blood. The technique used by the laboratory when studying these hormones is important. It is important that the laboratory is of good quality in order to evaluate these hormone tests correctly.
If testosterone will be measured in the blood in PCOS patients, combined oral contraceptives (COC) should be discontinued for at least 3 months. Because combined oral contraceptives increase sex hormone binding globulin and decrease gonadotropin-dependent testosterone production. If testosterone levels are high or the symptoms progress rapidly, the patient should be examined for ovarian or adrenal tumour or cancer.
When PCOS is diagnosed, the patient should be examined for cardiovascular diseases, regardless of age and body mass index.

If there is no pregnancy despite 6 months of regular sexual intercourse without protection at least 2 days a week, a detailed examination for infertility is recommended.

Examination;

• Hormone tests should be performed,
• The patency of the tubes should be checked by HSG (hysterosalpingography, medicated uterine film) or closed surgery and spermiogram test should be performed.

**If clomiphene citrate treatment will be given, it is not necessary to check tubal permeability before treatment. If the patient is resistant to this drug or if other treatments will be started, tubal permeability should be checked.

In PCOS, combined oral contraceptives (contraceptives) are the first drug treatment option for ovulation problems, menstrual irregularities and high levels of the male hormone androgens. However, these medications treat the symptoms of the disease, not the disease.

There is no definite treatment for polycystic ovary disease because the cause is not clear. However, it is possible to treat the symptoms caused by PCOS disease and prevent serious diseases that may be caused by PCOS disease in the future. In other words, treatment should be individualised according to the patient's complaints.

As it is very important in all areas of life, it is very important to make a healthy lifestyle change in PCOS patients, that is, to eat healthy (diet) and exercise regularly. Even losing 5-10% of the weight can lead to improvement in ovulation (ovulation) and male hormone excess findings, thus conception, decrease in hair growth and regularisation of menstruation. In addition, all diseases that obesity may cause in the future (such as diabetes, cardiovascular diseases, high cholesterol) are prevented in this way.

What are the dietary considerations?

First of all, a special diet programme should be applied on a patient basis to increase patient compliance; diet should be recommended considering the psychological, socioeconomic and socio-cultural level of the patient.

• Foods with low glucose content (brown sugar, wholemeal flour, wholemeal pasta, dried legumes, fruits (except melon, watermelon, banana), oats) should be preferred.
• Fibre foods: bulgur, oats, whole wheat bread, fresh and dried fruits should be preferred.
• Frequent and intermittent feeding: It is important to feed every 3 hours to reduce hunger pangs.
• Processed foods should be avoided
• Low-fat or lean meats should be consumed

It is also important to avoid alcohol and smoking and to reduce the level of stress in life.

In addition to these, treatment should be planned for the symptoms of the disease in polycystic ovary patients. These are

1. Infertility treatment in PCOS patients who want to have children: As a primary treatment, if menstruation is not regularised despite weight loss with diet and exercise or ovulation problem persists, it is recommended to start treatments such as clomiphene citrate or letrazole to increase egg development and ovulation. (More studies are needed for letrazole in terms of reliability). If pregnancy cannot be achieved with these treatments, gonadotropin hormone can be given as a secondary treatment (intrauterine vaccination treatment can be performed together with it) or laparoscopic ovarian drilling surgery can be performed. If pregnancy cannot be achieved with these treatments, IVF/ICSI (in vitro fertilisation) is recommended as a tertiary treatment.

The choice of treatment should be completely personalised. The age of the patient, the presence of other factors that may cause infertility, the patience of the couple, the success of previous treatments are important in the treatment decision.

Weight loss in PCOS patients leads to improvement in reproductive and metabolic factors as well as a decrease in complications seen in pregnancy. Since weight loss with the use of weight loss drugs or bariatric surgery may cause preterm delivery and low birth weight babies, weight loss with lifestyle changes should be the first option.

As an additional treatment, some therapies to overcome insulin resistance and reduce insulin levels increase clinical pregnancy rates in PCOS patients. Metformin is used for this purpose. However, studies have reported that live birth rates do not change with metformin treatment. Therefore, metformin use is recommended in PCOS patients with diabetes or insulin resistance. Nevertheless, metformin is recommended in gonadotropin timed intercourse treatment because it reduces the duration of treatment, increases the response to treatment, and reduces the dose of gonadotropin treatment. Metformin does not reduce the rate of miscarriage or multiple pregnancy. The use of metformin during IVF/ICSI (microinjection) treatment does not increase the live birth rate, but it can reduce the risk of OHSS (ovarian hyperstimulation syndrome), which is the most feared side effect in IVF treatment, and since it directly affects the endometrium (fertility bed), it increases implantation, that is, the attachment of the embryo to the uterus.
Aromatase inhibitors: Letrazole: Reduces the level of estrogen by blocking the aromatase enzyme that converts androgens to estrogens in the ovaries. Low estrogen level increases the release of gonadotropins from the hypothalamus and pituitary regions of the brain, leading to egg development and ovulation. Letdrazole has a more favourable effect on the endometrium, i.e. the fertile bed, than clomiphene citrate. However, further research is needed for its safety.

1. Regardless of age and body mass index, PCOS patients with impaired glucose tolerance, impaired fasting glucose or type 2 diabetes should be treated and preventive measures should be taken for diabetes. In PCOS patients with insulin resistance and elevated insulin hormone, drug therapy that breaks insulin resistance such as Metformin can be started. It would be better to manage the treatment process together with the endocrine specialist. In PCOS patients without diabetes, blood glucose levels should be checked at intervals of 1-3 years and precautions should be taken (preferably 75 gram Oral Glucose Tolerance Test should be performed). Existing insulin tests have limited clinical significance and are not recommended for routine follow-up. In patients who cannot use combined contraceptives (COCs), metformin can be used for hair growth and excess weight.
2. In case of menstrual irregularities, hormone therapy such as contraceptives may be recommended. If menses are late and menstruation is not regular, uterine thickening and increased risk of uterine cancer may be observed in the future.
3. In case of complaints of acne (acne), hair loss and increased hair growth: In addition to contraceptives, some alternative medicines are recommended. These drugs are anti-androgen drugs (spirenolactone, cypreterone acetate, finasteride, flutamide...) which have the effect of lowering the male hormone testosterone. If, despite 6 months of POP and cosmetic treatment, the complaint of hair growth has not disappeared, anti-androgenic drugs are recommended.
4. Blood pressure should be measured annually, cholesterol values should be analysed at certain intervals and treatment should be given in cases of high cholesterol.
5. It is not clear when anxiety and depression should be screened, but this condition should be evaluated at certain intervals. The first-line treatment is psychological therapy, but antidepressant or anxiolytic treatments may be planned in patients deemed necessary.
6. Anti-obesity drug treatment: Drugs such as liraglutide, semaglutide, glucagon like peptide-1 (GLP-1) receptor agonist and orlistat should be recommended after weighing the profit and loss relationship.

It is still an experimental treatment in infertility treatments.

Even if it is not effective in ovulation, weight problems or hair growth, many studies indicating improvement in metabolic conditions are available in the literature. However, the evidence on the effects on ovulation, clinical pregnancy and live birth is not yet sufficient. Side effects and safety are not yet known for certain.

All exercises that enable weight loss or weight control are recommended. Preferred exercises are 150-300 minutes of moderate intensity aerobic exercise or 75-150 minutes of heavy intensity exercise or an equal combination of these and muscle strengthening exercises.

In adolescents, 60 minutes of moderate-heavy intensity physical activity per day, at least 3 days a week, which strengthens muscle and bone is recommended.

Physical activity is any body movement that is produced by skeletal muscles and requires energy expenditure. Leisure-time physical activity includes transport (e.g. walking or cycling), occupation (e.g. work), housework, play, sport or planned exercise, or activities in the context of daily, family and community activities.

Aerobic activity is recommended daily for at least 30 minutes at 10-minute intervals.

It is a closed-method surgery in which 8-10 holes are drilled into the ovaries with monopolar cautery (electrical energy). It may be preferred in some PCOS patients resistant to treatment. However, it is a secondary treatment because surgery with anaesthesia is required. After this procedure, spontaneous pregnancy formation with intercourse should be tried for up to 6 months. After the 6th month, if pregnancy cannot be achieved, it is recommended to resort to IVF method.

OHSS is ovarian hyperstimulation syndrome. It is very important to adjust the dose of egg enlargement drugs we give in infertile patients in this respect. It is possible to take precautions and prevent OHSS complication with some treatments. OHSS is a disease condition characterised by growing follicles turning into cysts, disrupting the hormone balance, fluid leakage from the vessels and fluid accumulation in the body, which can even cause the death of the expectant mother. Therefore, it is important that the treatment of PCOS patients is managed by an experienced infertility specialist. In order to prevent this condition, some medications should be added to the treatment, the dose of gonadotropin treatment should be kept low, and in patients with OHSS risk, gonadotropin anologues should be used as the last maturation (cracking) needle and frozen embryo transfer should be planned.

Frozen embryo transfer is a more successful and safer treatment method for PCOS patients.

Routine use of metformin is not recommended in patients with PCOS. However, it can be used in some indications.

These treatments may be recommended after weighing the benefit and harm, but they are not a first-line recommendation.

There is no treatment that completely eliminates PCOS disease. Cysts cannot be treated with drugs or surgery because PCOS is actually not a cyst, but a condition in which there are too many follicles in the ovaries, that is, sacs that will develop eggs, and this excessive number of sacs disrupts the hormone balance. As a treatment, it is possible to treat the symptoms caused by PCOS.

Treatment must be individualised according to the patient. There is no single type of treatment.