IVF complications are pathological conditions directly caused by the implementation of the in vitro fertilization program. The forms of complications depend on the etiological factor and include ovarian hyperstimulation syndrome, bleeding, infection, ectopic pregnancy, thrombosis, fetoplacental insufficiency, early termination of gestation, premature birth. Diagnostics includes anamnesis collection, general and gynecological examination, ultrasonography, culdocentesis, blood tests. Treatment is most often conservative, surgery is necessary for urgent gynecological conditions.
N98 Complications related to artificial insemination
Assisted reproductive technologies involve aggressive hormone therapy, invasive intervention, therefore they are associated with a number of undesirable side effects. Complications can occur at different stages of in vitro fertilization – during follicle puncture (in 0.5% of women), after oocyte sampling (in a third of patients), after embryo transplantation into the uterine cavity (ectopia of the fetal egg develops in 2-10% of patients). After IVF, multiple pregnancies are recorded 30-40 times more often than in the population, accompanied by a significant increase in the likelihood of complications of pregnancy and childbirth, which gives grounds to attribute multiple gestation to pathological conditions.
IVF complications are associated with iatrogenic effects – the intake of high doses of gonadotropins into the body, trauma, infection of blood vessels and tissues during transvaginal puncture of the ovary, transplantation of several embryos at once in order to increase the likelihood of a successful outcome of the procedure. There are also a number of risk factors for side effects (primarily pathologies that caused infertility):
- Gynecological and somatic status. Polycystic ovary syndrome, tendency to allergic reaction, thrombophilia increase the likelihood of developing systemic pathology. Rough scars, adhesions in the pelvic area, inflammatory diseases of the genitals are risk factors for traumatic injuries, infection during egg collection, as well as implantation disorders.
- Physiological features. Ovarian hyperstimulation syndrome (OHSS) is more often observed in the presence of eight or more antral follicles on the second day after menstruation, asthenic physique, in young (under 30 years old) women. However, thrombotic complications of IVF (both on the background of OHSS and isolated) occur more often in patients older than 35 years.
- The drugs used. Ovarian stimulation or support of the luteal phase with human chorionic gonadotropin (hCG) more often leads to systemic complications. It is believed that it is this exogenous hormone that triggers the pathological process.
The mechanism of IVF complications associated with hyperovulation stimulation has not been definitively studied. Previously, it was believed that OHSS was caused by an abnormally high concentration of follicular phase estrogens, but now this hypothesis has been refuted. It is assumed that hyperstimulated ovaries produce a certain factor that leads to increased vascular permeability and the formation of transudate in the abdominal, pleural cavity, and the unknown factor is closely related to the immune system, since follicular fluid, blood plasma and peritoneal effusion of patients contain a large amount of cytokines.
Under the influence of activation of the renin-angiotensin system with the participation of cytokines, the permeability of ovarian vessels increases, which leads to transudation. Due to the increasing filtration of the liquid part of the blood, hypovolemia and related disorders develop: violation of water-electrolyte metabolism, arterial hypotension, hemoconcentration, hypercoagulation, oliguria. The ovaries increase due to the formation of multiple cysts, edema, which leads to their hypermobility. If an embryo has been implanted, all disorders are aggravated due to the production of endogenous HCG by the ovary.
Controlled ovarian stimulation leads to insufficiency of the luteal phase formed by the feedback principle, hyperestrogenism, progesterone deficiency and, as a consequence, to inadequate structural and receptor gravidar transformation of the endometrium. The result is implantation disorders, and as pregnancy progresses, incomplete invasion of the trophoblast, fetoplacental insufficiency.
Infertility treatment by IVF consists of a number of components that can cause undesirable consequences. Pathology can manifest itself immediately after the procedure or delayed, therefore, pregnancy that occurred after the use of artificial insemination technique belongs to a high-risk group. Thus, side effects can be divided into complications related to:
Preparation for IVF
The consequences may be the result of prolonged intensive hormone therapy or traumatic effects during ovarian puncture:
- Complications of hormone treatment. The most common side effect is OHSS, manifested by an increase in the ovaries, ascites, hydrothorax, multiple organ failure. The mild form of the pathology occurs in 20-30% of patients, medium and severe – in 2-3%. Thrombotic complications (as a rule, thrombosis of the veins of the upper extremities, head, neck) are observed with a frequency of 0.1% (in combination with OHSS – 0.4%). Increased mobility of the ovary can lead to its torsion, apoplexy.
- Complications of follicle aspiration. Extremely rare problems associated with injury during puncture. Include external or internal bleeding (0.2-0.5%), infection or exacerbation of infection (0.02%).
After IVF, the risk of ectopic location of the fetal egg increases significantly, and 1.7% of patients develop heterotopic pregnancy (one embryo in the uterine cavity, the other outside it). Implantation often occurs too low, which entails placenta previa. Implantation of several transplanted embryos is also considered undesirable due to the high risk of subsequent complications.
The course of pregnancy after IVF
Obstetric complications even with singleton gestation after in vitro fertilization are often observed. Gestosis (65%), retrochorial hematoma (30%), fetoplacental insufficiency (19%), premature birth (17-67%), spontaneous abortions (17-30%) are usually recorded. 65% of pregnancies end with the birth of live children.
The earliest manifestations (during the first week after follicle aspiration) are due to the IVF preparation protocol. The mild and moderate form of OHSS proceeds without deterioration of general well-being, accompanied by pulling pains, a feeling of heaviness, tension and overflow of the abdomen. Severe OHSS develops more often in the case of implantation of the fetal egg (a week or more after the puncture), proceeds with pronounced weakness, swelling, a sharp increase in abdominal volume and body weight, shortness of breath, palpitations.
In case of injury to the vessel during puncture, complicated by internal bleeding, there is intense abdominal pain, pallor, dizziness, fainting. The development of iatrogenic infection is accompanied by serous, purulent, bloody, often unpleasant-smelling whites, pulling pain in the lower abdomen, an increase in body temperature.
Within three months after the puncture, thrombotic complications may develop (more often 4 weeks after egg collection), torsion and rupture of the ovary. Manifestations of venous thrombosis: swelling, pain, redness of the skin along the affected vessel. Ovarian lesions are characterized by sharp, unbearable abdominal pain, shock. The same signs are accompanied by an interrupted ectopic pregnancy.
Pregnancy complications can be observed at any time and are accompanied by a variety of symptoms. In the first trimester, these are bloody vaginal discharge (retrochorial hematoma), cramping pains and bleeding (threat of interruption). In the late stages – signs of gestosis: edematous syndrome, symptoms of arterial hypertension (headache, “flies” in front of the eyes), pain in the epigastric region, transient visual impairment.
Diagnostic search is carried out under the guidance of a gynecologist-reproductologist, obstetrician-gynecologist. The study begins with a clinical examination, during which it is possible to suspect OHSS, rupture, ovarian torsion, ectopic pregnancy according to information about IVF in the anamnesis, analysis of patient complaints, results of palpation, percussion. To clarify the diagnosis, a series of laboratory, instrumental studies are prescribed:
- Radiation methods. Ultrasound of the pelvic organs allows you to identify ectopic pregnancy, to assume OHSS by enlarged ovaries. With the help of ultrasound and the pleural cavity, it is possible to detect free fluid with moderate and severe complications of ovarian stimulation.
- Laboratory tests. Clinical blood analysis (high hematocrit, hemoglobin, thrombocytosis), biochemical examination (electrolyte imbalance, hypoproteinemia), coagulogram indicators indirectly confirm OHSS. An increase in the beta-subunit of hCG in the blood, urine indicates an ectopic pregnancy.
- Puncture of the Douglas space. Culdocentesis is used to diagnose internal bleeding (vessel injury during follicle aspiration, apoplexy, ovarian torsion). Cytological analysis of the punctate makes it possible to exclude ovarian adenocarcinoma.
If necessary, echocardiography and pelvic MRI are prescribed. Differential diagnosis of IVF complications is carried out with spontaneous abortion, cystic drift, acute adnexitis. The severe form of OHSS is differentiated with pathologies of the kidneys, lungs, stomach, blood vessels, and other diseases that have clinical similarities with the syndrome of systemic inflammatory response – sepsis, acute appendicitis, acute pancreatitis. It may be necessary to consult an oncogynecologist, an abdominal surgeon, as well as a cardiologist, a nephrologist.
Therapeutic tactics depend on the nosological form of pathology, the severity of its course. Complications that occur easily are treated on an outpatient basis. In moderate and severe forms, hospitalization in a hospital is necessary. Critical, life-threatening disorders are treated in the intensive care unit. Conservative methods are more often used, in some cases surgical intervention may be required.
Diet. In case of OHSS, a diet rich in proteins, copious drinking with a high salt content (mineral water) is prescribed. In the case of gestosis, on the contrary, proteins in the diet and the amount of fluid consumed are limited.
- Medical treatment. For analgesia, antispasmodics, analgesics are used. In order to correct vital functions, infusion therapy is prescribed. In case of an infectious complication of puncture and in order to avoid secondary infection with OHSS, antibiotics are used. Methotrexate is used for conservative treatment of persistent ectopic pregnancy.
- Evacuation of fluid from body cavities. Indications for laparocentesis are tense ascites, for puncture of the pleural cavity – a hydrothorax that makes breathing difficult. Emptying of the abdominal cavity is performed in small volumes with subsequent replenishment of proteins, which are rich in evacuated ascitic fluid.
- Surgical treatment. Emergency surgical intervention is required in case of interrupted tubal pregnancy, torsion, rupture of the ovary. If possible, organ-preserving treatment is carried out. In a severe, life-threatening condition, termination of pregnancy is indicated.
Prognosis and prevention
The prognosis of IVF complications for a woman is usually favorable, severe consequences are noted in less than 0.1%, a fatal outcome (usually associated with OHSS) occurs in one case out of several tens of thousands. Preventive measures begin at the stage of pre-pregnancy preparation: at least 2-3 months before the implementation of the IVF program, a thorough examination of the couple is carried out with subsequent treatment of infectious diseases, correction of hormonal and coagulation disorders.
To prevent torsion and rupture of the ovary, it is necessary to limit physical activity in the first half of gestation. With the threat of OHSS, embryo transfer is postponed until the next cycle. In order to avoid multiple births, according to modern standards of USA reproductology, one or two, in exceptional cases three embryos are transferred to the uterus. Secondary prevention consists in careful observation of an obstetrician-gynecologist throughout pregnancy.