In cases of recurrent unsuccessful IVF attempts, two main factors should be examined: embryo quality, including the quality of gametes such as sperm and eggs, and maternal-related factors. Maternal-related factors may include uterine and tubal anomalies or pathologies, immune system problems, and coagulation disorders. Problems related to embryo, sperm, or egg quality may stem from genetic causes, environmental factors, lifestyle habits, and nutrition. Therefore, subsequent IVF treatments are individualized according to the patient.
With the current advancements in IVF treatments, the success rate of achieving pregnancy is around 60%, and the most important factor influencing success is the woman’s age. If a couple has not achieved pregnancy after two treatment attempts, it should be considered recurrent failure, and certain evaluations should be conducted before initiating a new treatment.
In couples with embryo quality issues, if there is a male-related cause, sperm DNA fragmentation tests may be performed. However, in subsequent attempts, measures that may help improve embryo quality include quitting smoking, losing weight if overweight, maintaining a balanced diet, increasing the intake of antioxidant-rich foods, and the use of certain supportive vitamins.
The most important contribution is smoking cessation. Sometimes, even if embryo quality appears very good in the laboratory, its genetics may be abnormal. For this reason, in cases with two unsuccessful attempts, genetic testing of both partners should be requested. In the next attempt, embryo transfer may be performed after genetic evaluation of the embryo using methods such as PGT or microarray (aCGH). Monitoring embryo development within an embryoscope may also be beneficial in better assessing embryo quality in future attempts.
Maternal-related causes may include undetected uterine anomalies (such as septum, polyps, fibroids, adhesions) or anatomical issues such as fluid accumulation in the tubes (hydrosalpinx). After failed attempts, a thorough uterine imaging test should be conducted to investigate these pathologies, and if necessary, endoscopic procedures such as hysteroscopy or laparoscopy should be performed before a new treatment attempt.
Tests related to the mother’s coagulation system, immune system, or hormonal status should also be performed, and if any issues are identified, they should be corrected before proceeding with a new treatment.
In couples with previous unsuccessful attempts, the goal in subsequent treatment should be to reach the blastocyst stage (day-5 embryo) whenever possible. Embryos that reach the blastocyst stage have the highest implantation potential. The probability of pregnancy with a good-quality blastocyst is at least 30–40%.
Methods aimed at increasing embryo implantation, such as co-culture, laser-assisted hatching, the use of adhesive media known as embryoglue, or pregnancy vaccines, have not demonstrated clear benefits in studies and are often used with a “let’s try this as well” approach. Therefore, in such couples, the objective should be to thoroughly evaluate both partners and achieve a high-quality blastocyst in optimal laboratory conditions for transfer into the uterus.
There are also conflicting opinions regarding the routine use of blood-thinning injections, estrogen-containing medications, and aspirin after embryo transfer in cases with recurrent failures. While some practices use them routinely, others do not unless there is an underlying coagulation disorder. Therefore, treatment should be individualized based on patient evaluation.
