IVF at Advanced Maternal Age
At advanced maternal age, the most important factor affecting the success of IVF treatment is the woman’s ovarian reserve. If an adequate response to medications cannot be obtained due to decreased ovarian reserve, the chance of success with IVF treatment significantly declines.
Every woman is born with a finite number of eggs, and this number gradually decreases over the years. During menopause, there are no remaining egg cells in the ovaries. As a woman’s age increases, the likelihood of conceiving naturally or through treatment decreases markedly due to the reduction in egg number.
The average age of patients applying to IVF clinics has increased over the years. Advancing maternal age negatively affects both egg quality and quantity, thereby reducing the chance of pregnancy. With increasing age, the number of eggs carrying chromosomal abnormalities increases, leading to a higher risk of miscarriage. In pregnancies at advanced maternal age, conditions such as hypertension, gestational diabetes, and preterm birth are also more frequently observed.
The effect of male age on IVF success remains controversial; however, pregnancy rates tend to be lower in partners of older men. Studies have reported a slight increase in the incidence of autism, schizophrenia, and retinoblastoma in cases of advanced paternal age.
IVF Treatment at Advanced Maternal Age
There is currently no treatment method capable of increasing ovarian capacity. The benefits of non–evidence-based treatments are very limited, and most involve significant costs. The benefit of using very high doses of medication is also controversial. Short protocols are preferred for ovarian stimulation in IVF treatment. Although the doses of ovarian-stimulating drugs may be higher than those used in normal responders, excessively high doses are not recommended. In cases with a low number of eggs, intracytoplasmic sperm injection (ICSI) is preferred as the fertilization method.
When IVF with mild stimulation is mentioned, antagonist protocols involving the combined use of low-dose daily ovarian-stimulating drugs and medications that prevent premature ovulation should be considered. In some cases, medications containing clomiphene or letrozole may also be added. It has also been suggested that low-dose treatments may have beneficial effects on egg quality, embryo development, and the endometrium (uterine lining).
In natural cycle IVF, the natural development of the egg is monitored by ultrasound, and egg retrieval is performed just before ovulation occurs. This is not always possible, as in some women the egg may ovulate spontaneously due to signals from the brain before retrieval.
Studies comparing IVF treatments using low-dose versus high-dose medications have reported live birth rates per cycle of 16% in low-dose treatments and 24% in conventional IVF treatments. Cycle cancellation rates are higher in the low-dose group (18% vs. 8.3%). In natural cycle applications, cancellation rates are very high (reported between 27% and 71%), resulting in lower ongoing pregnancy rates (0%–6.1%). Based on these results, natural cycle IVF is recommended as an effective treatment option only for women whose ovaries no longer respond to medication.
Hydrosalpinx (Blocked Fallopian Tube Filled with Fluid)
Hydrosalpinx refers to the closure of the finger-like projections at the end of the fallopian tube, called fimbriae, resulting in fluid accumulation within the tube. It usually occurs as a result of tubal infections or endometriosis. The most common cause of infection is chlamydia.
The presence of hydrosalpinx during IVF treatment reduces the chance of pregnancy. Live birth, pregnancy, and implantation rates are lower, while miscarriage and ectopic pregnancy rates are higher. In such patients, the damaged tube should either be surgically removed or blocked in a way that prevents it from affecting the uterine cavity before starting IVF treatment.
If hydrosalpinx is detected during ovarian stimulation, all embryos should be frozen, the hydrosalpinx surgically treated, and frozen embryo transfer performed afterward.
A detailed evaluation should be carried out before starting treatment to detect hydrosalpinx. Medical history, chlamydia antigen testing, transvaginal ultrasound, and hysterosalpingography are useful diagnostic tools. If hydrosalpinx is not treated surgically, IVF success rates decrease by approximately 50%.
Endometrioma (Chocolate Cyst)
Endometriosis is observed in 25% of patients who are unable to conceive. Among patients undergoing IVF, 5–10% have unilateral or bilateral endometriomas. Endometriomas reduce ovarian reserve and response to treatment. The presence of endometriosis increases the frequency of tubal blockage. Surgical treatment of chocolate cysts before IVF does not increase pregnancy rates; therefore, IVF treatment is recommended first.
If endometriomas are smaller than 3 cm, IVF is recommended. However, for cysts larger than 3–4 cm, laparoscopic removal may be considered. Surgery should be avoided in patients with previous ovarian surgery, bilateral cysts, or low ovarian reserve.
Polycystic Ovary Syndrome
Polycystic ovary syndrome is present in approximately 15% of patients undergoing IVF treatment. These patients have an increased risk of excessive response to ovarian stimulation drugs and ovarian hyperstimulation syndrome (OHSS). Ultrasound typically shows a characteristic polycystic ovarian appearance. If insulin resistance is present, medications such as metformin are prescribed, and weight control is recommended. Ovarian stimulation is initiated with low-dose medications. These patients also have increased risks of gestational diabetes and hypertension during pregnancy.
The main goal of treatment in patients with PCOS is to reduce the risk of OHSS. Metformin therapy may reduce the risk of OHSS. It is recommended to use 850 mg tablets twice daily from day 20 of the previous menstrual cycle until the day of egg retrieval.
Congenital Uterine Anomalies
Congenital Uterine Anomalies
They are observed in 2–3% of the population. The group with the lowest live birth rates (50–55%) consists of patients with a complete uterine septum. Hysteroscopic resection of the septum is recommended. Rates of first- and second-trimester miscarriages are increased, as well as risks of preterm birth and abnormal fetal presentations such as breech or transverse lie.
Surgical correction is no longer recommended in cases of double uterus, except in very rare situations. In patients with a double uterus undergoing IVF, single embryo transfer is the most appropriate approach to reduce the risk of pregnancy loss and preterm birth. Embryo transfer should preferably be performed into the larger uterine cavity.
Asherman Syndrome (Intrauterine Adhesions)
Approximately 40% of patients with Asherman syndrome present with infertility. Intrauterine adhesions negatively affect IVF success and are a cause of recurrent IVF failure. Hysterosalpingography, ultrasound, and hysteroscopy are useful diagnostic methods.
Hysteroscopic adhesiolysis is the gold standard treatment. In cases of severe adhesions, multiple hysteroscopic procedures may be required. Adhesions often recur. To reduce recurrence, estrogen therapy, intrauterine balloon placement, or hyaluronic acid gel may be used.
Fibroids
Fibroids are observed in 20–40% of women. Removal of submucosal fibroids (located beneath the endometrium) increases pregnancy rates in IVF, whereas surgical treatment of subserosal fibroids (located on the outer uterine wall) has no effect on pregnancy outcomes.
Intramural fibroids located within the uterine wall should be surgically treated if they compress the uterine cavity or are larger than 5 cm.
Uterine artery embolization is not recommended for women with infertility.
Thrombophilia
Thromboembolism is a rare complication of hormonal ovarian stimulation in IVF treatment, occurring due to clot formation within blood vessels. Hormonal therapy causes significant changes in coagulation and fibrinolytic systems. Its incidence is approximately 1.6 per 100,000 cycles. Most reported cases occur in the presence of underlying thromboembolic risk factors.
All patients should be evaluated for personal risk factors before treatment. Thrombophilia screening should be performed in patients with a personal or family history of thrombosis or embolism, and in those who develop ovarian hyperstimulation syndrome during IVF.
Prophylactic anticoagulant therapy should be initiated in patients with a history of deep vein thrombosis, OHSS, or confirmed thrombophilia. To avoid bleeding complications, anticoagulants should be started 24 hours after egg retrieval. If pregnancy occurs, treatment should continue until the end of the first trimester. In patients diagnosed with thrombophilia, prophylaxis should be continued throughout pregnancy.
Couples Carrying Hepatitis B/C
The risk of mother-to-child transmission in IVF is not different from that in natural pregnancies. In HBsAg-positive men, ICSI and sperm washing techniques appear to be safe options.
Women Carrying HIV
Women who are untreated or unaware of their HIV status may transmit the virus to their partners or children. If fallopian tubes are patent, natural conception is possible, but unprotected intercourse carries a risk of transmission to the male partner. Therefore, assisted reproduction is safer.
IVF treatment should be performed when the viral load is as low as possible. IVF for these couples must be carried out in centers with specially equipped laboratories to ensure isolation from other patients.
IVF Patients with Psychosexual Problems
Patients with vaginismus are advised to receive sexual therapy before IVF. Through sexual development programs, patients explore their behaviors and sexuality, helping them feel more comfortable with their bodies and sexuality.
In these patients, egg retrieval and embryo transfer procedures are performed under general anesthesia. For luteal phase support, progesterone may be administered via injection instead of the vaginal route.