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IVF at Advanced Maternal Age
The key factor affecting the success of IVF treatment at advanced maternal age is the woman's ovarian reserve. If the response to medication is insufficient due to a decline in ovarian reserve, the chance of success in IVF treatment drops noticeably.
Every woman is born with a certain number of egg cells, and this number gradually decreases over the years. By menopause, no egg cells remain in the ovaries. As a woman's age advances, the chance of having a child either spontaneously or through treatment decreases significantly as the number of eggs declines.
The average age of patients applying to IVF clinics has risen over the years. As a woman ages, this negatively affects both the quality and the number of her eggs, reducing the chance of pregnancy. With age, the number of eggs carrying chromosomal abnormalities increases, and along with it, the risk of miscarriage rises. Problems such as high blood pressure, gestational diabetes, and preterm birth are also more common in pregnancies at advanced maternal age.
The effect of paternal age on IVF success is debated, but pregnancy rates are lower among the partners of older men. Studies have reported a small increase in the incidence of autism, schizophrenia, and retinoblastoma when paternal age is advanced.
IVF Treatment at Advanced Maternal Age
No treatment method has yet been found that can increase ovarian capacity. The benefits of treatments that are not evidence-based are quite limited, and most of them also carry significant costs. The benefit of using high-dose medication is also debated. Short protocols are preferred for ovarian stimulation in IVF. Although the dose of egg-stimulating medications is higher than in normal responders, going to very high doses is not recommended. When the number of eggs is low, ICSI is preferred as the fertilization method.
When referring to low-dose (mild stimulation) IVF, this generally means antagonist protocols that combine daily low-dose egg-developing medication with medication that prevents premature ovulation. Sometimes medications containing clomiphene and letrozole may also be added to this regimen. It is also said that low-dose treatments may have beneficial effects on egg quality, the embryo, and the endometrium (the uterine lining).
In the natural cycle approach, the egg's natural development is monitored by ultrasound and retrieval is performed just before ovulation occurs. This is not always possible. In some women, signals from the brain can trigger spontaneous ovulation before the egg retrieval procedure.
In studies comparing IVF treatment using low-dose versus high-dose medication, the live birth rate per cycle was found to be 16% with low-dose treatment versus 24% with classic IVF treatment. Cycle cancellation rates were higher in the low-dose medication group, at 18% versus 8.3%. In natural cycle applications, the cancellation rate of treatment has been reported to be very high, between 27% and 71%. Accordingly, ongoing pregnancy rates are low (0%-6.1%). Based on these results, the natural cycle is recommended as an effective treatment option only for women whose ovaries no longer respond to medication.
Hydrosalpinx (Blocked Tube with Fluid Buildup)
Hydrosalpinx is the closure of the finger-like projections called fimbriae at the end of the tubes, leading to fluid accumulation inside the tube. It occurs as a result of tubal infection or endometriosis. The most common cause of the infection is chlamydia.
The presence of hydrosalpinx during IVF treatment reduces the chance of pregnancy. Live birth, pregnancy, and implantation rates are lower, while pregnancy loss and ectopic pregnancy rates are higher. In such patients, before starting IVF, either the damaged tube should be removed or it should be blocked in a way that will not affect the uterine cavity.
If detected during ovarian stimulation, all embryos should be frozen, the hydrosalpinx should be surgically treated, and the frozen embryos should then be transferred.
A detailed examination should be carried out before starting treatment to detect hydrosalpinx. History, chlamydia antigen testing, vaginal ultrasound, and hysterosalpingography are useful for diagnosis. If hydrosalpinx is not treated surgically, IVF success will drop by roughly half.
Endometrioma (Chocolate Cyst)
Endometriosis is seen in 25% of patients who are unable to have children. Among patients applying for IVF, 5-10% have one-sided or two-sided chocolate cysts. Endometriomas reduce ovarian reserve and the response to treatment. In the presence of endometriosis, the frequency of tubal blockage increases. Surgical treatment of chocolate cysts before IVF does not increase pregnancy rates. For this reason, proceeding directly to IVF treatment is recommended first.
If chocolate cysts are smaller than 3 cm, IVF is recommended. However, in the presence of cysts larger than 3-4 cm, laparoscopic removal of the cysts is considered. Surgery is avoided in patients who have previously had surgery, who have cysts on both sides, or who have low ovarian reserve.
Polycystic Ovary Syndrome
Polycystic ovary syndrome is present in 15% of patients undergoing IVF treatment. These patients have an excessive response to ovary-stimulating medication and an increased risk of ovarian hyperstimulation syndrome (OHSS). On ultrasound, the ovaries show a typical polycystic appearance. If insulin resistance is present, medications such as metformin are given and weight control is recommended. Ovarian stimulation treatment is started with low-dose medication. These patients also carry increased risks of high blood sugar and elevated blood pressure during pregnancy.
In patients with polycystic ovaries, the goal of treatment is to reduce the risk of OHSS. Metformin treatment can reduce the risk of OHSS. It is recommended to use an 850 mg tablet, twice daily, from the 20th day of the previous menstrual cycle until the day of egg retrieval.
Congenital Uterine Anomalies
Congenital Uterine Anomalies
These are seen in 2-3% of the population. The group with the lowest live birth rates, at 50-55% frequency, is the group with a complete septum inside the uterus (uterine septum). Cutting the septum with the help of hysteroscopy is recommended. Miscarriage rates are increased in the first and second trimesters. The risks of preterm birth and breech or transverse fetal position during delivery are also increased.
Surgery is no longer recommended for cases of double uterus. However, in very exceptional circumstances, these operations can still be performed. In patients with a double uterus undergoing IVF treatment, transferring a single embryo is the most appropriate approach to reduce the risk of pregnancy loss and preterm birth. The transfer procedure should preferably be performed into the larger of the two uterine cavities.
Asherman Syndrome (Intrauterine Adhesions)
40% of Asherman Syndrome cases present with the complaint of infertility. Intrauterine adhesions negatively affect IVF success and are one cause of repeated IVF failure. Hysterosalpingography (a contrast X-ray of the uterus and tubes), ultrasound, and hysteroscopy are examination methods that can be useful.
Opening the adhesions with hysteroscopy is the gold standard. In cases with severe adhesions, hysteroscopy may need to be performed more than once. In most cases, the adhesions will recur. To reduce the risk of recurrence, estrogen treatment, an intrauterine balloon, or hyaluronic acid gel may be applied.
Fibroids
Fibroids are seen in 20-40% of women. Removing submucosal fibroids (those beneath the endometrium) increases pregnancy rates in IVF, while surgical treatment of subserosal fibroids — those growing on the outer wall of the uterus — has no effect on pregnancy outcomes.
Surgical treatment is recommended for intramural fibroids located within the uterine wall if they press on the uterine cavity or are larger than 5 cm.
Uterine artery embolization (blocking the artery leading to the uterus with special agents) is not a recommended treatment option for patients who are unable to have children.
Thrombophilia
Thromboembolism (vascular blockage due to clot formation within a blood vessel) is a rare complication of hormone-based ovarian stimulation during IVF treatment. During hormone treatment, significant changes occur in the clotting and clot-dissolving systems. Its frequency is approximately 1.6 per 100,000 cycles. Most of the thromboembolism cases reported in the literature occur in the presence of risk factors related to thromboembolic disease.
All patients should be evaluated for their personal risk factors before starting treatment. Thrombophilia screening should always be performed in patients with a personal or family history of intravascular clotting or embolism, and in patients who develop ovarian hyperstimulation syndrome during IVF treatment.
Preventive treatment with blood-thinning medication (thromboprophylaxis) should be started in patients with a history of deep vein thrombosis, those who develop hyperstimulation, or those with thrombophilia. To avoid causing possible bleeding, blood-thinning medication should be started 24 hours after the egg retrieval procedure. If pregnancy occurs, treatment should be continued until the end of the first trimester. In patients diagnosed with thrombophilia, prophylaxis should be continued throughout the entire pregnancy.
Couples Carrying Hepatitis B/C
Besides the risk of transmitting the disease to the partner or child, there is also a risk of transmitting the disease from patient samples to laboratory personnel. Hepatitis B and C infection has no effect on pregnancy outcomes. A baby born to a mother who is HBs-Ag positive must be vaccinated immediately; for hepatitis C, there is not yet a vaccine.
The risk of transmission from mother to baby in IVF is no different from that in a normal pregnancy. In HBs-Ag positive men, ICSI and sperm-washing techniques appear to be a safe option.
Women Carrying the HIV Virus
Women who have not received any treatment, or who are unaware that they carry the virus, can transmit the disease to their partner and children. If the tubes are open, pregnancy may occur through natural intercourse, but there is also a risk of transmitting the disease to the man through unprotected intercourse. For this reason, IUI is a safer option.
IVF treatment should be carried out during the period when the viral load is, if possible, at its lowest. IVF for these couples should be performed at IVF centers with specially equipped laboratories. This is particularly important in terms of isolating the laboratory from other couples.
IVF Patients With Psychosexual Problems
Patients with vaginismus are advised to undergo sexual therapy before IVF. Through a sexual development program, the patient is helped to explore her own patterns of behavior and sexuality, so that she can feel more at peace with her body and her sexuality.
In these patients undergoing IVF, egg retrieval and embryo transfer are performed under general anesthesia. Progesterone for luteal phase support can be given by injection instead of the vaginal route.