Female infertility

Female infertility is the inability of a woman to conceive during her childbearing years.

A marriage is considered infertile if, despite regular sexual activity and the absence of contraception, pregnancy does not occur within 1 year.

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Epidemiology

The frequency of infertile marriages is 15-17%, of which female infertility accounts for 40-60%. The most common forms of female infertility are tubal-peritoneal (50-60%) and anovulatory (endocrine) (30-40%) forms, as well as external genital endometriosis (25%); combined forms of infertility account for 20-30%. In 2-3% of cases, the cause of infertility cannot be determined.

In each area of the reproductive system of the male and female body, pathological processes can occur that disrupt the complex biological mechanism of their work and lead to infertility.

Primary and secondary infertility are distinguished. Primary infertility is infertility in women (or men) who have regular unprotected sexual intercourse and do not conceive (infertile sperm in men). Secondary infertility is the absence of pregnancy (ability to fertilize in men) within a year of regular sexual intercourse after previous pregnancies. Absolute infertility is infertility associated with the absence or abnormal development of the genitals.

The presence of various forms of infertility in one of the partners is defined as combined infertility; the presence of infertility factors in both partners is a combined form of infertility in a couple.

One of the most important problems in gynecology and reproductive medicine is infertility. Infertility, which accounts for 15% of married couples in Russia, is associated with the problem of the childless future of millions of citizens, the reduction and loss of the nation's gene pool. Perhaps. this problem is more relevant than many others in medicine, because only after the birth of a person can we talk about the importance and significance of providing him with this or that medical care.

• Reproductivity is the ability to reproduce individuals similar to oneself, ensuring the continuity and succession of life.
• Reproductive health is defined by WHO as the absence of diseases of the reproductive system or disorders of reproductive function with the ability to carry out reproductive processes with complete physical, mental and social well-being.
• Sexual health is a combination of physical, emotional and social aspects of sexual life that positively enriches the personality, promotes mutual understanding and love.
• Family planning is a set of socio-economic, legal, and medical measures aimed at the birth of healthy children desired by the family, the prevention of abortions, the preservation of reproductive health, and the achievement of harmony in marriage.
• Fertility is the ability to reproduce offspring.
• Sterility is the lack of ability to reproduce offspring.
• Infertile marriage is the absence of pregnancy during 12 months of regular sexual intercourse without the use of any means of contraception, provided that the spouses (sexual partners) are of childbearing age (WHO).

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Causes female infertility

Female infertility can be a consequence of many diseases and conditions.

Primary infertility in women

• Genital infantilism, abnormal development of female genital organs.
• Disorders of regulation of hormonal function of the ovaries, functional insufficiency of the sex glands.
• Diseases of the uterus and uterine appendages that prevent pregnancy.

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Secondary infertility in women

• Inflammatory diseases of female genital organs, complications after abortions, IUDs.
• Diseases of the endocrine system.
• Tumors of the genital organs.
• Ectopic pregnancy.
• Somatic diseases (tuberculosis, collagenoses, blood diseases, etc.).
• Traumatic injuries of the vagina, cervix, perineum.
• Chronic intoxication (alcohol, nicotine, heavy metal salts, etc.).
• Industrial and professional factors (microwave field, low doses of ionizing radiation).
• Malnutrition.

The main cause of female infertility is inflammatory diseases of the female genital organs or their consequences (in 60-70% of cases). Among inflammatory processes, infertility is most often accompanied by inflammation of the uterine appendages, which causes obstruction of the fallopian tubes, various disorders of the functional state of the ovaries.

Obstruction of the fallopian tubes occurs especially often with gonorrheal salpingitis, but can also be a consequence of non-specific inflammation. Infertility often occurs after an abortion or pathological birth. Abortion can result in salpingitis with the development of obstruction of the fallopian tubes and damage to the uterine mucosa.

Salpingitis leads not only to obstruction of the fallopian tubes, but also to disruption of their motor activity, to dystrophic changes in the mucous membrane of the fallopian tube, which prevent fertilization.

Inflammation of the ovaries can disrupt ovulation, due to which the egg does not enter the abdominal cavity, and when adhesions form around the ovary (in the case of normal ovulation), it cannot enter the tube. In addition, oophoritis can disrupt the endocrine function of the ovaries.

The role of endocervicitis in the etiology of infertility is significant, as it changes the function of the epithelium of the cervical canal. Colpitis can also be a cause of infertility (changes in the properties of vaginal fluid against the background of various diseases can lead to the death of spermatozoa).

In the etiology of infertility, endocrine disorders occur in 40-60% of cases. In this case, the function of the ovaries may be impaired primarily, which is observed in case of abnormalities in the development of the genital organs or in case of damage to the follicular apparatus of the ovaries due to infectious diseases or intoxications (the process of maturation of the egg and ovulation is impaired, the hormonal function of the ovaries, necessary for maturation, transport of the egg and its fertilization, is reduced).

Infantilism and hypoplasia of the genitals can be the cause of infertility in women. In this case, infertility is promoted by both anatomical and functional features of the reproductive system associated with its underdevelopment (long narrow vagina with a shallow posterior fornix, narrow cervical canal, decreased hormonal function of the ovaries, incomplete cyclic processes in the endometrium, dysfunction of the fallopian tubes, etc.).

Ovarian function may change secondarily due to diseases of the pituitary gland, thyroid gland, and adrenal glands. Infertility is caused by diseases such as myxedema, hypothyroidism, severe forms of diabetes mellitus, Itsenko-Cushing's disease, obesity, etc.

Infertility can be caused by injuries and displacements of the genital organs (old perineal rupture, gaping of the genital slit, drooping of the vaginal walls, bends and displacements of the uterus, eversion of the cervix, urogenital fistulas, adhesions of the uterine cavity, cervical canal closure).

In some cases, infertility is a concomitant symptom of endometriosis and tumors of the female genital organs.

General diseases and intoxications (tuberculosis, syphilis, alcoholism, etc.), as well as poor nutrition, vitamin deficiency, mental illnesses cause complex disorders leading to ovarian dysfunction, which can also lead to infertility.

The cause of infertility is immunological factors (the formation of antibodies to sperm in a woman’s body).

Frequency of detection of various factors of reproductive dysfunction in married couples.

Factors of infertility	Frequency of detection
Men's	37%
Women (total)	82%
of which:
hormonal	56%
cervicovaginal	51%
tuboperitoneal	48%

It should be taken into account that among women suffering from infertility, more than 60% have two or more factors of impaired fertility.

Abnormal cervical mucus

Abnormal cervical mucus may impair fertility by inhibiting penetration or increasing sperm destruction. Normal cervical mucus changes from thick, impenetrable to thinner, clearer, and stretchable as estradiol levels increase during the follicular phase of the menstrual cycle. Abnormal cervical mucus may remain impenetrable to sperm at the time of ovulation or may cause sperm destruction by facilitating the entry of vaginal bacteria (eg, as in cervicitis). Occasionally, abnormal cervical mucus contains antibodies to sperm. Abnormal mucus rarely significantly impairs fertility except in cases of chronic cervicitis or cervical stenosis resulting from treatment for cervical intraepithelial neoplasia.

Women are examined for cervicitis and cervical stenosis. If they do not have either of these conditions, a postcoital cervical mucus test is performed to check for infertility.

Reduced ovarian reserve

Diminished ovarian reserve is a decrease in the quantity or quality of oocytes, leading to decreased fertility. Ovarian reserve may begin to decline in the 30s and earlier and declines rapidly after age 40. Ovarian lesions also reduce reserve. Although older age is a risk factor for decreased ovarian reserve, both age and decreased ovarian reserve are themselves indicators of infertility and result in lower treatment success.

Tests for decreased ovarian reserve are indicated for women over 35 years of age who have had ovarian surgery or have failed ovarian stimulation with exogenous gonadotropins. The diagnosis is suspected if FSH levels are greater than 10 mIU/mL or estradiol levels are less than 80 pg/mL daily three times during the menstrual cycle. The diagnosis can be made by giving the woman clomiphene 100 mg orally once daily on days 5–9 of the menstrual cycle (clomiphene citrate confirms the test). A significant increase in FSH and estradiol levels from days 3–10 of the cycle indicates decreased ovarian reserve. In women over 42 years of age or if ovarian reserve is decreased, donor oocytes may be used.

Other causes of female infertility

• Problems with ovulation

A menstrual cycle lasting less than twenty-one days and more than thirty-five days may signal the inability of the egg to be fertilized. If ovulation does not occur, the ovaries are unable to produce mature follicles, and therefore, eggs that can be fertilized. This is one of the most common causes of female infertility.

• Ovarian dysfunction

Disruption of hormone production in the hypothalamus-pituitary system can sometimes cause dysfunction of the ovaries. Luteotropin and follitropin are produced either in very large or very small quantities, and their ratio is disrupted, and as a result, the follicle does not mature sufficiently, the egg is non-viable or does not mature at all. The cause of such dysfunction can be a head injury, a tumor, or other disorders in the lower cerebral appendage.

• Hormonal imbalance

Hormonal imbalance in the body can lead to the disappearance of menstruation or non-maturation of the egg. This disorder has many causes, including genetic predisposition, previous infectious diseases, weakened immune system, endocrine diseases, surgical interventions and injuries to the abdominal organs and genitourinary system.

• Genetic predisposition

Female infertility can be caused by genetic factors, hereditary predisposition, in which the egg cannot mature.

• Polycystic ovary syndrome

In polycystic disease, follicle stimulating hormone production decreases, while luteotropin, estrogen, and testosterone levels remain normal or exceed them. It is believed that decreased follicle stimulating hormone levels cause insufficient development of the follicles produced by the ovaries. As a result, multiple follicular cysts (up to six to eight millimeters) are formed, which are diagnosed by ultrasound. The affected ovary is usually enlarged, and a white capsule forms on its surface, through which the egg cannot pass, even if it is mature.

• Cervical canal disorders

As a result of such disorders, spermatozoa are unable to penetrate the mucous membrane of the uterus, which causes their death.

• Cervical erosion

The cause of female infertility may be such a pathology as erosion - ulcerative formations on the mucous membrane of the cervix, which can be congenital or occur due to infections and injuries. The development of pathology is facilitated by hormonal disorders, menstrual cycle failure, early onset of sexual relations, lack of a regular sexual partner, weak immunity. As a rule, such pathology is asymptomatic and is determined during examination by a gynecologist. Sometimes there may be brown discharge from the genitals and pain during intercourse.

• Scars on the ovarian lining

This pathology leads to the ovaries losing the ability to produce follicles, resulting in the absence of ovulation. Scars may appear after operations (for example, when removing cysts) and infectious pathologies.

• Unruptured follicle syndrome

In this syndrome, the mature follicle does not rupture and transforms into a cyst. The causes of this disorder may be hormonal imbalances, thickening of the ovarian capsule or pathology of its structure. However, this phenomenon has not been fully studied.

• Endometriosis

With this disease, endometrial cells begin to grow and form polyps that penetrate not only the fallopian tubes and ovaries, but also the abdominal cavity. This disease does not allow the egg to mature and prevents it from merging with the sperm, and in the case of fertilization, it prevents the egg from attaching to the uterine wall.

• Psychological factor

Frequent stressful situations can lead to disruption of natural physiological functions, which has a negative impact on the fertilization process. Psychological factors also include female infertility of unknown origin (approximately ten percent of couples do not have any disorders that provoke female infertility).

• Pathology of the uterine structure

Any deformations of the uterus have an effect similar to the IUD - they prevent the egg from attaching to the endometrium. Such pathologies include polyps and uterine myoma, endometriosis, and congenital structural pathologies.

Diagnostics female infertility

When conducting diagnostics, it is necessary to examine both partners regardless of the complaints presented. First of all, it is necessary to exclude the presence of sexually transmitted diseases, hereditary pathologies and diseases of the endocrine system. After all the necessary information about the presence or absence of concomitant diseases has been collected, the patient is examined for secondary sexual characteristics, a rectal examination is performed and an examination of the pelvic organs is carried out.

Diagnostic procedures also include hysterosalpingography (performed on the sixth to eighth day from the beginning of the cycle). Hysterosalpingography is used to determine the condition of the uterine cavity and tubes. They are filled with a contrast agent through the cervical canal. If the fallopian tubes have normal patency, this solution is not retained in them and penetrates into the abdominal cavity. Hysterosalpingography can also be used to diagnose other uterine pathologies. To diagnose the disease, they also use ultrasound biometry of follicle growth (on the eighth to fourteenth day of the cycle), hormonal testing (luteotropin, follitropin, testosterone - on the third to fifth day of the cycle), progesterone levels are determined on the nineteenth to twenty-fourth day of the cycle, and an endometrial biopsy is performed two to three days before the onset of menstruation.

Diagnosis of infertility involves examination of both sexual partners; diagnostic measures must be carried out in full to identify all possible factors of infertility in both the woman and the man.

In accordance with WHO recommendations, when examining infertile women, the following should be established and carried out: When studying the anamnesis:

• number and outcomes of previous pregnancies: spontaneous and induced abortions, including criminal ones; ectopic pregnancy, hydatidiform mole, number of living children, postpartum and post-abortion complications;
• duration of primary or secondary infertility;
• methods of contraception used and the duration of their use after the last pregnancy or in case of primary infertility;
• systemic diseases: diabetes, tuberculosis, diseases of the thyroid gland, adrenal cortex, etc.;
• drug treatments that may have a short-term or long-term negative effect on ovulation processes: cytotoxic drugs and X-ray therapy of the abdominal organs; psychopharmacological agents such as tranquilizers;
• operations that could contribute to the development of infertility: appendectomy, wedge resection of the ovaries, operations on the uterus, and others; the course of the postoperative period;
• inflammatory processes in the pelvic organs and sexually transmitted diseases, type of pathogen, duration and nature of therapy;
• endometrioid disease;
• nature of vaginal discharge, examination, treatment (conservative, cryo- or electrocoagulation);
• the presence of discharge from the mammary glands, their connection with lactation, duration;
• production factors and the environment – epidemic factors; alcohol abuse, taking toxic substances, smoking, etc.;
• hereditary diseases, taking into account relatives of the first and second degree of kinship;
• menstrual and ovulatory history; polymenorrhea; dysmenorrhea; first day of the last menstrual period;
• sexual function, pain during sexual intercourse (dyspareunia).

Objective examination

• height and body weight; weight gain after marriage, stressful situations, climate change, etc.;
• development of mammary glands, presence of galactorrhea;
• hairiness and its distribution; skin condition (dry, oily, aspae vulgaris, striae);

Examination of body systems:

• blood pressure measurement;
• X-ray of the skull and sella turcica;
• fundus and visual fields.

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Gynecological examination data

During a gynecological examination, the day of the cycle corresponding to the date of the examination is taken into account. The degree and features of the development of the external genitalia, the size of the clitoris, the nature of hair growth, the features of the vagina, cervix, uterus and appendages, the condition of the sacrouterine ligaments, the presence and nature of discharge from the cervical canal and vagina are assessed.

Colposcopy or microcolposcopy is a mandatory examination method during the first examination of a patient, it allows to identify signs of colpitis, cervicitis, endocervicitis and erosion of the cervix, which can cause infertility and be a sign of chronic genital infection.

Laboratory and instrumental examination methods

Of great importance in the correct diagnosis of infertility in women is the implementation of additional laboratory and instrumental examination methods. Compliance with the timing of the main methods of examination of women allows to avoid false-positive and false-negative results of these studies. WHO recommends the following frequency and timing of laboratory examination of women with infertility:

• functional diagnostic tests – 2-3 cycles;
• hormonal studies (LH, FSH, prolactin, testosterone, DHEA) on the 3rd–5th day of the menstrual cycle; in the middle of the cycle and in the second phase;
• hysterosalpingography on the 6th–8th day of the menstrual cycle; kympertubation – on the days of ovulation;
• Ultrasound biometry of follicle growth on the 8th-14th day of the menstrual cycle;
• immunological tests – on the 12th-14th day of the menstrual cycle.

Immune forms of infertility are caused by the development of antisperm antibodies, more often in men and less often in women.

One of the tests that can suggest immunological incompatibility is the postcoital test (PCT), known as the Sims-Huner test or the Shuvarsky test. The test allows indirectly assessing the presence of antisperm antibodies. The most significant clinical manifestation of immunological disorders is the presence of specific antibodies to spermatozoa. In women, antisperm antibodies (ASAT) can be present in the blood serum, cervical mucus and peritoneal fluid. The frequency of their detection ranges from 5 to 65%. The examination of a married couple should include the determination of antisperm antibodies already at the first stages and primarily in the husband, since the presence of antisperm antibodies in the ejaculate is evidence of the immune factor of infertility.

Postcoital test (Shuvarsky-Sims-Huner test) – is performed to determine the number and motility of spermatozoa in cervical mucus. Before the postcoital test, partners should abstain from sexual intercourse for 2-3 days. Spermatozoa moving forward can be detected in cervical mucus within 10-150 minutes after sexual intercourse. The optimal interval before the test should be 2.5 hours. Cervical mucus is collected with a pipette. If, with normozoospermia, 10-20 moving spermatozoa can be seen in each field of vision, then the cervical factor can be excluded as a cause of infertility.

Determination of antisperm antibodies in women in cervical mucus: on preovulatory days, mucus is collected from the cervical canal for quantitative determination of antibodies of three classes - IgG, IgA, IgM. Normally, the amount of IgG does not exceed 14%; IgA - 15%; IgM - 6%.

• laparoscopy with determination of fallopian tube patency – on the 18th day of the menstrual cycle;
• determination of progesterone levels on the 19th-24th day of the menstrual cycle;
• endometrial biopsy 2-3 days before the onset of menstruation.

A comprehensive clinical and laboratory examination of women in an infertile marriage allows us to identify the following causes of infertility:

• Sexual dysfunction.
• Hyperprolactinemia.
• Organic disorders of the hypothalamic-pituitary region.
• Amenorrhea with elevated FSH levels.
• Amenorrhea with normal estradiol levels.
• Amenorrhea with reduced estradiol levels.
• Oligomenorrhea.
• Irregular menstrual cycle and/or anovulation.
• Aiovulation with regular menstruation.
• Congenital anomalies of the genital organs.
• Bilateral obstruction of the fallopian tubes.
• Adhesive process in the pelvis.
• Endometrioid disease.
• Acquired pathology of the uterus and cervical canal.
• Acquired obstruction of the fallopian tubes.
• Tuberculosis of the genital organs
• Iatrogenic causes (surgical interventions, medications).
• Systemic causes.
• Negative postcoital test.
• Unspecified causes (when laparoscopy was not performed).
• Infertility of unknown origin (when using all examination methods, including endoscopic ones).

Treatment female infertility

Treatment of female infertility should first of all be aimed at eliminating the main cause that provokes reproductive function problems, as well as at correcting and eliminating any accompanying pathologies. Simultaneously with the main treatment, general strengthening procedures and psychocorrection are carried out. Treatment of women must be comprehensive in order to restore normal functioning of the reproductive system as soon as possible.

In case of obstruction of the fallopian tubes, anti-inflammatory therapy is carried out, which is aimed not only at eliminating the inflammatory process and restoring the patency of the fallopian tubes, but also at activating the functions of the hypothalamus-pituitary-ovary system. Physiotherapeutic methods of treatment include radon or hydrogen sulphide baths, the use of therapeutic mud. To correct the functioning of the body's immune system, antihistamines (suprastin, tavegil, diphenhydramine), immunomodulatory drugs are prescribed. Treatment is carried out with small doses of drugs for two to three months or shock doses for a week.

Women with obstruction or complete absence of fallopian tubes, as well as diseases such as polycystic disease, endometriosis, etc., may be offered the method of in vitro fertilization. The woman is prescribed drugs to enhance the growth and maturation of eggs. Then, a special needle is used to extract the mature eggs and fertilize them in a test tube. On the third to fifth day, the embryos are placed in the uterus, and the patient is prescribed special drugs to ensure that the embryos take root. Two weeks after the procedure, a blood test is prescribed to determine whether the pregnancy is developing. An ultrasound examination is performed on the fifth to sixth week.

It should be noted that female infertility is caused by more than twenty reasons. Therefore, in order to carry out correct treatment, a thorough and sometimes long-term examination is necessary to identify the reasons that prevent a woman from getting pregnant. Only after a detailed and complete diagnosis can the attending physician prescribe qualified treatment, which is strictly individual in each case.

The goal of infertility treatment in women is to restore reproductive function.

The main principle of infertility treatment is early identification of its causes and consistent implementation of treatment stages.

Modern highly effective methods of infertility treatment include medicinal and endoscopic methods and methods of assisted reproductive technologies. The latter are the final stage of infertility treatment or an alternative to all existing methods.

Therapy tactics depend on the form and duration of infertility, the patient's age, and the effectiveness of previously used treatment methods. If traditional treatment has not had a positive effect for 2 years, it is advisable to use assisted reproductive technology methods.

The choice of treatment methods for infertility and the determination of their sequence in each specific case depend on factors such as the duration of the disease, the severity of changes in the fallopian tubes, the extent of the adhesion process, the age and somatic condition of the patient.

Treatment of tubal-peritoneal infertility

Treatment of tubal infertility with organic lesions of the fallopian tubes is quite difficult. Among conservative methods, the priority today is complex anti-inflammatory, resorption treatment, carried out against the background of exacerbation of the inflammatory process. The therapy carried out consists of inducing an exacerbation of the inflammatory process according to indications, followed by complex antibacterial and physiotherapy, sanatorium and spa treatment.

Reconstructive tubal microsurgery, introduced into gynecological practice in the 1960s, became a new stage in the treatment of tubal infertility, allowing such operations as salpingo-ovariolysis and salpingostomatoplasty to be performed. Improvements in endoscopic techniques have made it possible to perform these operations during laparoscopy in some cases. This method also allows diagnosing other pathologies of the pelvic organs: endometriosis, uterine fibroids, ovarian cysts, polycystic ovary disease, etc. The possibility of simultaneous surgical correction of the pathology detected during laparoscopy is very important.

Treatment of endocrine infertility

The therapy prescribed to patients with endocrine forms of infertility is determined by the level of damage to the hormonal regulation system of the ovulation process. Based on a certain level, the following groups of patients with hormonal forms of infertility are distinguished:

The 1st group is extremely polymorphic, conventionally united by the common name - "polycystic ovary syndrome". This group is characterized by an increase in LH in the blood, normal or increased FSH levels, an increase in the ratio of LH and FSH, and a normal or decreased level of estradiol.

Treatment should be selected individually and may consist of several stages:

• the use of estrogen-gestagen drugs according to the principle of "rebound effect";
• the use of indirect ovarian function stimulants – clomiphene citrate (clostilbegyt).

In the presence of hyperandrogenism, it is prescribed in combination with dexamethasone;

• use of direct ovarian stimulants - metrodin hCG.

Group 2 – patients with hypothalamic-pituitary dysfunction.

Women with various menstrual cycle disorders (luteal phase deficiency, anovulatory cycles or amenorrhea), with pronounced secretion of estrogens by the ovaries and low levels of prolactin and gonadotropins. The sequence of use of drugs that stimulate ovulation in this group of patients is as follows: gestagen-estrogen drugs, clomiphene citrate (clostilbegyt), possibly in various combinations with dexamethasone, parlodel (bromocriptine) and/or hCG. If ineffective - menopausal gonadotropins, hCG.

Group 3 – patients with hypothalamic-pituitary insufficiency. Women with amenorrhea, who have little or no ovarian estrogens; prolactin levels are not elevated, gonadotropin levels are low or cannot be measured. Treatment is possible only with menopausal gonadotropins hCG or LH-RH analogues.

Group 4 – patients with ovarian failure. Women with amenorrhea, in whom estrogens are not produced by the ovaries, the level of gonadotropins is very high. Until now, infertility treatment in this group of patients has been futile. Hormonal replacement therapy is used to relieve subjective sensations in the form of "hot flashes".

Group 5 – women who have high prolactin levels. This group is heterogeneous:

• patients with hyperprolactinemia in the presence of a tumor in the hypothalamic-pituitary region. Women with various menstrual cycle disorders (luteal phase deficiency, anovulatory cycles or amenorrhea), elevated prolactin levels, and a tumor in the hypothalamic-pituitary region. In this group of patients, it is necessary to distinguish patients with pituitary microadenoma, for whom treatment with parlodel or norprolact is possible under careful supervision of an obstetrician-gynecologist, neurosurgeon and ophthalmologist, as well as patients with pituitary macroadenomas, who should be treated by a neurosurgeon, either by radiotherapy of the pituitary gland or by tumor removal;
• patients with hyperprolactinemia without damage to the hypothalamic-pituitary region. Women with menstrual cycle disorders similar to the subgroup with clear production of ovarian estrogens, increased prolactin levels. The drugs of choice for this form are parlodel and norprolact.

Treatment of immunological infertility

To overcome the immune barrier of cervical mucus, the following are used: condom therapy, non-specific desensitization, some immunosuppressants and assisted reproduction methods (artificial insemination with the husband’s sperm).

Assisted Reproduction Methods

In cases where treatment of infertility in a married couple using conservative therapy methods and, if necessary, surgical treatment does not bring the desired results, it is possible to use assisted reproduction methods. These include:

• Artificial insemination (AI):
  • husband's sperm (IISM);
  • donor sperm (IISD).
• In vitro fertilization:
  • with embryo transfer (IVF PE);
  • with oocyte donation (IVF OD).
• Surrogacy.

The use and application of these methods is in the hands of specialists in reproductive medicine and family planning centers, but practicing physicians should know the possibilities of using these methods, indications and contraindications for their use.

Assisted reproductive technologies involve manipulation of sperm and eggs in vitro to create an embryo.

Assisted reproductive technologies (ART) can result in multiple embryo pregnancies, but the risk is lower than with controlled ovarian hyperstimulation. If the risk of genetic defects is high, the embryo should be screened for defects before implantation.

In vitro fertilization (IVF) can be used to treat infertility due to oligospermia, sperm antibodies, tubal dysfunction, or endometriosis, as well as unexplained infertility. The procedure involves controlled ovarian hyperstimulation, oocyte retrieval, fertilization, embryo culture, and embryo transfer. Clomiphene in combination with gonadotropins or gonadotropins alone can be used for ovarian hyperstimulation. GnRH agonists or antagonists may often be used to prevent premature ovulation.

After sufficient follicle growth, hCG is administered to induce final follicle maturation. 34 hours after hCG administration, oocytes are collected by follicle puncture, transvaginally under ultrasound control, or less commonly laparoscopically. In vitro oocyte insemination is performed.

The semen sample is typically washed several times with tissue culture medium and concentrated to increase sperm motility. Additional sperm are added, and the oocytes are then cultured for 2–5 days. Only one or a few of the resulting embryos are transferred into the uterus, minimizing the chance of multiple pregnancy, which is highest with in vitro fertilization. The number of embryos transferred is determined by the woman’s age and likely response to in vitro fertilization (IVF). Other embryos may be frozen in liquid nitrogen and transferred into the uterus in a subsequent cycle.

Gamete intrafallopian tube transfer (GIFT) is an alternative to IVF but is used infrequently in women with unexplained infertility or normal tubal function combined with endometriosis. Multiple oocytes and sperm are obtained in the same way as in IVF, but the transfer is performed transvaginally under ultrasound guidance or laparoscopically to the distal fallopian tubes where fertilization occurs. The success rate is approximately 25-35% in most fertility centers.

Intracytoplasmic sperm injection is used when other techniques have failed or when severe sperm dysfunction has been noted. Sperm is injected into an oocyte, and the embryo is cultured and transferred in a manner similar to in vitro fertilization (IVF). In 2002, more than 52% of all assisted reproductive technologies in the United States were performed using intracytoplasmic sperm injection. More than 34% of assisted reproductive technologies resulted in pregnancy, with 83% of live births.

Other procedures include a combination of in vitro fertilization and gamete intrafallopian transfer (GIFT), the use of donor oocytes, and the transfer of frozen embryos to a surrogate mother. Some of these technologies have moral and ethical issues (e.g., the legality of surrogacy, selective reduction in the number of implanted embryos in multi-embryonic pregnancies).