Polycystic Ovary Syndrome

Polycystic Ovary Syndrome is a set of symptoms characterized by irregular menstrual periods causing an increase in male hormones (leading to excess body and facial hair, acne, etc.) or the polycystic shape of the ovary on ultrasound. The symptoms are commonly witnessed in about 10-15% of the women of childbearing ages, and frequently occur from the early age of youths. They may temporarily disappear after the emergency at the early stage to occur again later. The symptoms range from simple irregular menstrual periods to all complications associated with the syndrome. Instead of full recovery, this syndrome should rather be continuously managed.

Causes and Mechanism

No exact causes are known for this syndrome. Complex actions including genetic factors or insulin resistance may be causes, and the disorder in the secretion of hormone that is induced by this syndrome cause diverse clinical patterns and complications. Insulin resistance is most commonly caused by obesity, and it can also be witnessed in thin women.

Symptoms

Complications of the Syndrome

1. Obesity
2. Diabetes (noninsulin dependent)
3. Cardiovascular disorders
4. Solenoma, Endometrial Hyperplasia

Tests Required for Diagnosis

No single-test is currently available for diagnosing the syndrome.

Treatment of the Syndrome

No single treatment method is currently available to completely cure the syndrome, but there may be diverse methods for controlling it. Such treatments can help improve the symptoms but if the treatments are suspended, the symptoms and the disorders in hormone secretions can recur, requiring continued treatment efforts to reduce the risk of the occurrence of complications.

Insulin Resistance and Polycystic Ovarian Syndrome

Currently, the exact cause of polycystic ovarian syndrome is not known but the syndrome is thought to be caused by complex actions of diverse causes as well as genetic factors. In recent years, insulin resistance is drawing an increased attention as one of the causes and, diabetes is actually being frequently found in the diagnostic process of the syndrome.

What is Insulin Resistance?

Insulin resistance is a condition in which insulin is not effectively used for controlling the level of sugar though it is normally secreted. Insulin resistance causes the human body to need more insulin for the normal control of sugar, resulting in higher levels of insulin in blood. This again causes to increase male hormones, which cause the characteristic symptoms like acne, anovulation and infertility.
The most common cause of insulin resistance is obesity, but it is also found in thin women as well. Insulin resistance causes metabolic syndrome which is characterized by diabetes and hyperlipidemia, and is an important risk factor for cardiovascular disorders and diabetes.

Treatment of Insulin Resistance - Metformin

As the relations between polycystic ovary syndrome and insulin resistance were revealed, insulin lowering drugs began to be used in the treatment of the syndrome, leading to a more fundamental treatment of the syndrome. The most commonly used drug is metformin, which is a blood sugar depressant for oral medication. Metformin enhances the reaction of insulin to lower the levels of blood sugar and insulin. This leads to lower levels of male hormones to improve diverse symptoms of polycystic ovary syndrome and prevent long-term complications. Additionally, a single treatment can induce normal ovulations and co-medication with other ovulation inducing agents can contribute to a higher possibility of pregnancy. Unlike ovulation inducing agents, however, it does not provide the risk of multiple births, and unlike other blood sugar lowering drugs, it actually provides no side effect of hypoglycaemia.
The most common side effects of metformin are the ones related to the digestive system including nausea, vomiting stomachache and diarrhea, and these symptoms can be mostly improved within several weeks from the start of treatments. As the improvement is proportional to the amount of drugs, the quantities can be gradually increased. In the patients of the disorders of the kidney, liver and lungs, there is an increased risk of complications, requiring consultation with the doctor prior to medication for the test including a blood test.

Conclusions

The most important thing in the control of polycystic ovary syndrome is the appropriate recognition and information about the syndrome. In this sense, attention should be continuously paid to the syndrome before and after childbirth, and continued consultations with the specialists in the field are also recommended.

Ovarian Dysfunction

The function of the ovary is directly related with a woman's age. The number of eggs the ovary contains at the time of her birth is already determined, and, as the number continues to decrease from the first menarche to menopause, the function of the ovary gradually decreases. The symptoms can be seen in the patients who have received anti-cancer treatment, radiotherapy, or the past General Surgery performed on the ovary, and the functions can also be affected by the past General Surgery that can reduce blood supply to the ovary, inflammation or, sometimes, smoking.

Predictive Test of the Ovarian Function

The tests for predicting the functions of the ovary include FSH test, estradiol value test, AMH test and ultrasound. The ultrasound test evaluates the ovarian function by counting the number of small follicles inside the ovary.

Symptoms

The lowered function of the ovary means a lower response to hyperovulation that is employed in in-vitro procedure. The results of the studies on the pregnancy rates of the patients with the lowered ovarian response differ, and one of the reasons is the fact that the ovarian dysfunction is not clearly defined yet. The related experts who participated in the expert meeting held in Bologna in 2010 agreed on the definitions of the ovarian dysfunction to the effect that a patient has the ovarian dysfunction if she satisfies at least two out of the following conditions:

Dealing with Ovarian Dysfunction

If the patient experienced lowered ovarian response in the past or did not show a positive response to the first IVF attempt, how should IVF be done? There is no single answer to this question.

The answer depends on the conditions of the patients including those who are predicted to show a normal response and need higher doses of injection for the response of hyperovulation.

In case the number of eggs do not exceed despite the IVF procedure, the only egg that is naturally ovulated is retrieved or an ovulation inducing agent is medicated while minimizing the use of injections.

As assistive alternatives, some dietary supplements and the injection of growth hormone are sometime used, and though these are not clinically tried, they still are helpful to some extent.

Necessity of Examining Male Infertility

In general, at least 15% of married couples are said to be suffering from infertility. Infertility is the inability to conceive a baby for at least one year despite normal sex life without contraception. In these couples, husbands are said to be responsible for about 50% of the causes of infertility. Therefore, in infertility cases, male infertility should be checked.

Causes of Male Infertility

Examination of Male Infertility

Treatment of Male Infertility

Good Habits for Healthy Pregnancy

1. Quit smoking
2. Reduce or quit alcohol consumption
3. Maintain normal weight
4. Avoid exposure to the environment in which the temperature of testicles rise, including sauna.
5. Avoid exposure to the diverse environmental hormones.

FAQ about Male Infertility

Definition of Artificial Insemination

Artificial insemination (AI) is the deliberate method of receiving semen from a husband in a woman's ovulation period, treating it with a special culture fluid, and then collecting only sperm with good motility and injecting it directly into a female's uterus through a thin tube.

Major Considerations For AI

What serves the most important role in natural conception is sperm having a good motility and a sufficient amount of cervical mucus. Therefore, the followings should first be considered:

In case sperm's motility is diminished or cervical mucus is not properly secreted due to cervical conization, and etc., AI is preferable than natural conception for a higher possibility of pregnancy.

AI may also be considered if natural conception does not occur for at least six months to one year despite no particular abnormalities found in the infertility exam.

AI and In-Vitro Fertilization (IVF)

As AI should be implemented inside the body, at least one fallopian tube should be properly functioning, and, IVF is strongly recommended when both tubes are blocked or any significant ovarian dysfunction or significantly lowered conditions of the sperm.

※ While AI may be conducted based on the natural menstrual cycle, hyperovulation is mostly used for a higher possibility of pregnancy. The rate of successful pregnancy per cycle is about 20%.

Definition of In-vitro Fertilization

In-vitro fertilization, or "in-vitro fertilization-embryo transfer" (IVF-ET) in full, is a process of fertilization in which an egg is taken out from a woman and, after its fertilization with sperm outside the body and embryo culture for 2-5 days, is transferred to the endometrium.

Procedure

Stage 1: Ovarian Hyperstimulation

In the natural menstrual cycle, one egg is ovulated a month. Ovarian hyperstimulation is the stimulation to induce development of multiple follicles of the ovaries for higher possibilities of pregnancy. The method of inducing ovulation is determined in consideration of diverse factors including the age and ovarian function of the patient, and the results of the past inducement.

Stage 2: Egg Retrieval and Sperm Prepration

Stage 3: In-Vitro Fertilization and Culture

Upon retrieval of the egg and sperm, they are put on a culture dish containing culture medium for fertilization. In general, it is left for natural fertilization, otherwise intracytoplasmic sperm injection (ICSI) is also opted. The fertilized embryo is cultured for about 3-5 days.

Stage 4: Embryo Transfer

The fertilized embryo is inserted to the endometrium using a catheter. The locations of the catheter and embryo are checked under abdominal ultrasound. Depending on the age of the patient, conditions of the embryo and number of days of culture, 1-3 embryos are transferred. No anesthesia is required, and the patient can return to normal daily life after taking a rest for about 10 minutes.

Stage 5: Luteal Support

Luteal support begins after egg retrieval. In most cases, progesterone agent or gonadotrophin agent is used, which can be injected, inserted through the vagina or orally administered. Luteal support contributes to the implantation of the embryo and embryogenesis.

Incubation of The Best Embryo For Transfer and Establishment of Selction System

iDream Clinic has introduced the incubation room having clean room facilities and the air shower system to completely block fine dust and provide the optimum atmospheric environment for in-vitro cultivation of the embryos.
The clinic also has G210 InviCell Long Term Incubator with individual chambers that help secure the individual incubation spaces for each embryo to achieve higher rates of pregnancy, and Primo Vision Time Lapse embryo monitoring system that allows for monitoring the growth stages of the embryo in the optimum conditions, contributing to the higher rates of pregnancy based on the best embryos selected.

Embryo Incubator with Individual Chambers

Establishment of Latest Embryo Culture System

Latest Embyo Incubator That Is Recently Introduced

1. Controls electromagnetism that occurs in the traditional incubators
2. Uses advanced temperature system to maintain the culture temperature cycle similar to human body
3. Individual cuture spaces for embryos are provided per patient to provide an environment that does not affect other embryos

And, considering the fact that the long term embryo culture method is being widely adopted in recent years, the culture method using ambient humidity helps prevent microbiosis of the embryos, and the individual embryo culture spaces contribute to preventing cross-infection.

Embryo Incubation Using the Latest Embryo Incubation System

1. Maintaining embryos in the best conditions
2. Such conditions contribute to higher rates of pregnancy

Time-Lapse Embryo Monitoring System

Last time-Lapse Image of the Embryos

Last time-Lapse Image

In checking the developmental stages of embryos using the conventional microscope, there have been limits to checking the division and morphological development of abnormal embryonic cells. As this time-lapse monitoring system is capable of checking the growth stages of embryos on a real-time basis, the best embryos for transfer can be selected, which contributes to higher rates of pregnancy.
Additionally, instead of having to regularly take out the embryos from the incubator to monitor the conditions in the past, the system allows for monitoring the developmental stage of embryos on a real-time basis using the monitor connected to the microscope that is inside the incubator, which contributes to block harmful substances entering from outside and reducing the stress caused by the changes in the environment.

Hydrosalpinx

A hydrosalpinx is a distended and blocked fallopian tube filled with serous or clear fluid, which interferes with natural conception. The substances secreted from the fluid also affect the conditions of the embryo and the uterus, causing infertility.
Some studies showed that removing the fallopian tube having hydrosalpinx contributes to a higher success rate of pregnancy, but diverse studies are being also conducted in relation to whether the fallopian tube should be removed regardless of the conditions of the tube.

Endometrial Stimulation

In IVF, one of the causes of repetitive failures of pregnancy despite transfer of a healthy embryo is the conditions of the endometrium. In recent years, studies are actively conducted regarding this issue, and one of the alternatives is to make a cut artificially on the endometrium to stimulate diverse active factors that promote growth of the endometrium.
More studies have yet to come to decide that the endometrial stimulation actually raises pregnancy rates, but the results so far reported show that a number of cases in which the pregnancy rates have been raised in the groups of people who failed in pregnancy despite repeated IVF procedures. However, as this is a procedure that can be easily performed, many studies are now in progress.

Gonadotropin-releasing Hormone Agonist

The consequences of providing gonadotropic hormone during the implantation phase are not clearly known. There are at least such hypotheses that gonadotropic hormone acts upon pituitary gland to promote the secretion of corpus luteum hormone, and this corpus luteum hormone acts upon endometrium, and directly acts upon the gonadotropic hormone receptor existing in endometrium to affect endometrium. Many studies in this area are now in progress.
However, a number of studies have asserted that providing gonadotropic hormone helps raise the success rate of IVF.

Hysteroscopy

Hysteroscopy is the most useful method of inspecting pathology in the uterine cavity by endoscopy with access through the cervix. This can be used to remove polys or adhesions which may not be readily detected with ultrasound in the case of repetitive implantation failures.

Normal Endometrium

Endometrial Polyp

Endometrial Myoma

Endometrial Adhesion

Definition of Recurrent Miscarriage

Recurrent miscarriage is defined as three or more consecutive pregnancy losses before 20 weeks of gestation. But in accordance with the recent studies showing that the risk of miscarriage in those who experienced two consecutive miscarriages is not different from the risk in those with three consecutive pregnancy losses, the examinations on recurrent miscarriage are currently conducted on the women who experienced two consecutive miscarriages.

Causes of Recurrent Miscarriage

Diagnosis and Treatment

Definition of Preimplantation Genetic Diagnosis

Definition of Preimplantation Genetic Diagnosis
Preimplantation genetic diagnosis or preimplantation genetic screening inspection is a clinical method of examining chromosome abnormalities or genetic diseases using the cytogenetic or molecular genetic method upon the fertilized eggs during the procedure of the assisted reproductive technique.
Preimplantation genetic diagnosis is employed in the patients with a family history having a risk of giving birth to a baby with chromosome abnormalities (mutual translocation or Robertsonian translocation) or severe monogenetic disorders, and a consultation with the specialist is required to determine whether the diagnosis can be employed or not.
Preimplantation genetic screening inspection is mostly employed in the senior patients or those who experienced recurrent miscarriages, and the inspection of numerical aberrations of chromosomes is typically performed. All of these methods are performed before implantation, and only the normally fertilized egg is implanted in the uterus to help give birth to a healthy baby.

Procedure of Preimplatation Genetic Diagnosis

Separation of Embryonic Cells

Cells are collected from the day-3 embryo (8-cell embryo) or the day-5 embryo (blastocyst) using the embryo micromanipulation technique. Collecting the cells from each embryo does not affect the generation and implantation of the embryo and gestation at all, and the collected blastocytes are used for a molecular cytogenetic examination before implantation.

Examination of Genetic Disorders and Chromosomes

This is the simplest method to diagnose the numerical aberrations of chromosomes in the embryo.
For the process, the FISH (fluorescence in situ hybridization) method by which the fluorescent probe is used is employed to conduct genetic examination. This genetic examination is mostly employed for, among the patients of subfertility, the relatively aged women and those who experience recurrent miscarriage or tend to lose pregnancy during in vitro fertilization. The numerical aberrations of chromosomes are checked mostly upon the X and Y sex chromosomes related to Turner's syndrome and Klinefelter's syndrome, chromosome 21 related to Down syndrome, chromosome 18 related to Edwards syndrome, chromosome 13 related to Patau syndrome, and etc.
The whole DNA is amplified from the embryonic cells that are collected using the recently developed WGA (whole genome amplification) technique, and the chromosomes are checked for aberration using the array CGH technique.

Advantages of the Above Methods

1. More prompt and accurate analyses of the entire chromosomes compared to FISH
2. Accurate diagnosis even in the single cells through the DNA amplification technique
3. Contributing to checking the normal chromosomes of the embryo in case one of the parents has balanced translocation
4. The increased rates of pregnancy by implanting the normal embryos only that are checked through the genetic examination

Fertility Preservation

All women are born with approximately one million reproductive cells. Of the cells, about 400-500 cells are ovulated from the first period to menopause, and the rest of the reproductive cells are gradually decreased in the number through apoptosis. As women age, the number of cells continues to decrease and menopause comes when these reproductive cells are depleted.
The number of reproductive cells begins to decrease at a faster pace after the age of 35, and the quality of ova also is also lowered. The index that reflects the number of the remaining reproductive cells is called the ovarian reserve, which can be evaluated through a blood test or ultrasound examination and is used as the index for childbearing capability.
As the ovarian reserve is already decreased several years before menopause, the fact that a woman has periods now does not necessarily mean that she can get pregnant. Therefore, healthy reproductive cells need to be protected before the ovarian reserve is reduced. In particular, a cancer patient who is receiving chemoradiotherapy must protect her fertility in advance. Also, due to the recent trend of late marriage, unmarried women, even if they are currently healthy, need to protect their reproductive cells in advance as the functions of the ovary can weaken.

Ovarian Reserve Exam

1. Ultrasound Exam
2. Hormone Exam (LH/FSH/E2)
3. Antimullerian Hormone (AMH) Exam

Those Who Need Fertility

1. With past experience of ovarian General Surgery
2. Having endometriosis
3. Having family history of premature menopause
4. Having to undergo radiotherapy due to a detected cancer
5. Women suspected of diminished ovarian function
6. All women who wish to preserve ovarian reserve

How to Preserve Fertility

Laparoscopy and Infertility

Laparoscopy is a useful means for checking the exact conditions of the fallopian tube. While it can also be used for checking pelvic adhesion or endometriosis, it needs anesthesia and is an invasive exam method. Therefore, it is not used as the primary exam means and is opted on when the patient has a disease that should be treated like hydrosalpinx

Treatment of Infertility

If the Fallopian Tube has Abnormalities

The fallopian tube is an important area where the union between the egg and sperm occurs. Abnormalities found here may require surgical treatment depending on the conditions, and if it is judged normal function of the tube may not be possible after General Surgery, IVF needs to be considered.

Cervical Adhesion and Hydrosalpinx

If the fallopian tube is adhered to the neighboring areas and only its tip is blocked, the tube should be opened. Hydrosalpinx acts to reduce the rate of pregnancy by half and can cause miscarriage, and therefore, when conducting IVF, tubal ligation or tubectomy is generally implemented for a higher rate of pregnancy.

Tuboplasty

If the fallopian tube is severely damaged or its ultrastructure is maintained, the function of the tube can be recovered by opening the blocked tip of the tube through tuboplasty. However, as tuboplasty can sometimes cause tubal pregnancy, IVF is more often conducted after tuboplasty if IVF has failed for multiple times.

Treatment of Endometriosis of Infertiflity Patient

In the treatment of uterine fibroid that occurred in the ovary of a patient of infertility, maintaining the functions of the ovary is most important, and, in principle, it should not be removed if its size is about 4cm in diameter. General Surgery may be considered if there is a risk of hysterorrhexis due to the location of endometriosis or the pain is significant, but the functions of the ovary can be lowered after General Surgery.

Treatment of Uterine Fibroid of Infertiflity Patient

Surgical treatment of uterine fibroid should be determined based on the size and location. In some cases, large submucosal uterine fibroid that changes the space inside the uterus or intramuscular fibroid is better to be removed using laparoscopy. Melting fibroids should be carefully selected as it can extend the uterus during pregnancy, causing rupture of the uterus.

About Hysteroscopy

Hysteroscopy is the inspection of the uterine cavity by passing a long and thin hysteroscope through the vagina and cervix. Prior to insertion of the hysteroscope, fluids are introduced to expand cavity to facilitate the diagnosis of intrauterine pathology which may not be clearly seen with the ultrasound waves the video monitor and a surgical intervention is performed using fine surgical instruments.

Indications of Hysteroscopy?

1. Check and treat uterus bleeding
2. Remove tumors from the endometrium
3. Remove the uterine septum
4. Check the causes of infertility
5. Remove the submucous uterine fibroid
6. Separate the uterine adhesions

Upon checking the above lesions, the surgical instrument is inserted through another path attached to the hysteroscope to precisely remove or burn the lesions only.

Diagnosis of Endometrial Tumor and Hysteroscopic General Surgery (Clinical Case)

1. Diagnosis: Inject physiological saline to examine the endometrial tumors using ultrasound examination
   Uterus, uterine cavity (central black area), tumors inside the uterus
2. Tumors inside the uterus checked on ultrasound waves after hysteroscopy
3. Procedure of hysteroscopic General Surgery

Surgical Procedures Per Type of Hysteroscope

Diagnostic hyteroscopy is performed using a fine hysteroscope without anesthesia, and usually takes about two to five minutes. Surgical hysteroscopy is performed under either general or local anesthesia, and, as it is finished within a short period of time, it does not require hospitalization and the patient can be discharged within 15-30 minutes after the General Surgery, allowing the patient to lead normal daily life from the next day. It is a relatively simple General Surgery involving no postoperative pain, while rarely the patient can suffer mild pain or stomachache, which can last from 30 minutes to eight hours. In most cases, the patient can get pregnant soon after the General Surgery.

Indications of Hysteroscopy

The lesions inside the uterus cause infertility, and the uterine anomaly and adhesions inside the uterine can cause recurrent miscarriages.
Hysteroscopic images of the uterine septum of the patient who experienced recurrent miscarriage

Complications of Hysteroscopic General Surgery

Hysteroscopic General Surgery can cause postoperative infection, uterine perforations, vaginal bleeding, imbalance in electrolyte due to excessive supply of fluids, etc.