Complications of controlled ovulation: Currently, the assisted reproduction community designs controlled ovulation protocols by estimating the patient’s responsiveness to ovulatory drugs based on information such as the patient’s ovarian reserve, age, and medical history of the infertile patient. However, because current techniques for assessing ovarian response are still very poor, the design of controlled ovulation protocols can sometimes be unsatisfactory, and over- or underestimation can sometimes occur. This procedure has the potential for the following complications and/or side effects that could affect further treatment with in vitro fertilization-embryo transfer
1. Side effects of gonadotropin-releasing hormone agonists (GnRHa)
Currently, when designing controlled superovulation protocols, GnRHa is generally used to suppress the pituitary gland and prevent the occurrence of endogenous LH peaks in order to improve pregnancy rates. However, the use of GnRHa may lead to the following side effects.
(1) Ovarian activation: if only a few follicles are activated, after ultrasound puncture, then the cycle may be continued; if multiple follicles are activated, then the cycle is cancelled.
(2) Inadequate pituitary suppression: if it occurs, increase the dose of GnRHa and continue treatment; if the suppression remains inadequate after increasing the dose, treatment needs to be stopped.
(3) The general timing of GnRHa injections begins at mid-luteal phase (before the onset of menstruation). Since pregnancy cannot be reliably diagnosed at this time, there is a risk of misuse of GnRHa during pregnancy, resulting in unpredictable fetal exposure to GnRHa.
2. Side effects of gonadotropin-releasing hormone antagonists
The main role of gonadotropin-releasing hormone antagonists is to inhibit the pituitary gland and prevent endogenous LH peaks from occurring in order to improve pregnancy rates. However, in some special cases, pituitary suppression can occur. If it does not improve after routine treatment, the cycle is cancelled.
3. Ovarian hyperstimulation syndrome (OHSS)
Clinically, the main symptoms are nausea, vomiting, abdominal distension, ascites, pleural fluid, ovarian enlargement, and electrolyte disturbance. Severe OHSS can be life-threatening, with an incidence of about 0.5-5%. To avoid this outcome, doctors will monitor the ovaries more intensively, but even then OHSS is still difficult to avoid completely. If it occurs, this cycle will be cancelled on a case-by-case basis.
4. Occurrence of premature LH peak and premature ovulation
Premature LH peak or ovulation occurs before the follicles mature. Premature LH peak or ovulation may occur in a small number of patients even if ovulation suppressants are routinely used during the ovulation promotion process. After the occurrence of premature LH peak, the egg quality is impaired and the pregnancy rate decreases.
5. Poor ovarian response
i.e., few follicles. If this occurs and the response is still poor after further treatment, the cycle is cancelled.
6.Abnormal follicular development or endocrinological changes unfavorable to pregnancy
7. Complications of egg retrieval surgery
Egg retrieval is a surgical procedure and complications such as organ damage, bleeding, infection and hematoma may occur, requiring open surgery in severe cases. In rare cases, empty follicle syndrome may occur and eggs may not be retrieved. The abnormal position of the ovaries makes egg retrieval difficult and reduces the rate of egg retrieval. To reduce the pain of the egg retrieval procedure, we routinely use intravenous anesthesia or analgesics and local anesthetics, in extremely rare cases, the use of these drugs can result in anesthetic accidents with serious consequences. After the egg retrieval procedure, adhesions to the pelvic and abdominal organs may occur.
8. Sperm retrieval difficulties may occur in men on the day of egg retrieval, and most of them can be successfully retrieved after routine treatment
Although fine needle testicular or epididymal puncture for sperm retrieval is generally safe, complications such as bleeding, infection, and impact on testicular function may still occur.
9. The semen parameters of men fluctuate greatly, and those of patients with oligospermia and weak sperm fluctuate even more significantly
If the husband’s semen parameters are abnormal on the day of egg retrieval, it is estimated that the fertilization rate obtained by conventional in vitro fertilization is low and single sperm microinjection within the oocyte plasma can be used instead to improve the fertilization rate.
10. Ovarian abnormalities
Some infertility is caused by egg abnormalities, which include impaired maturation and structural abnormalities of the egg, but unfortunately it is still not possible to predict in advance whether the egg is defective before egg retrieval. There is no effective treatment for infertility caused by egg abnormalities.
11. Fertilization abnormalities
These include low fertilization rate, non-fertilization and abnormal fertilization. If fertilization is impaired or the fertilization rate is low, remedial intracytoplasmic single sperm microinjection can be performed, but the normal fertilization rate is low, the embryonic development potential is poor, and the pregnancy rate after transfer is low. The safety of this fertility technique is unknown because the eggs are already aging when remedial intracytoplasmic single sperm microinjection is performed.
12. Abnormal embryo development
These include fertilized eggs without oogenesis, delayed embryonic development, multiple embryonic fragments, and abnormal embryo division. At present, it is not possible to treat them.
13.Embryo transfer difficulties
It is generally rare and mainly occurs in patients with cervical dysfunction such as cervical canal malformation and tight inner cervical opening.
14.Pregnancy problem
Pregnancies obtained through in vitro fertilization-embryo transfer have the same problems as natural pregnancies, such as miscarriage, preterm birth, stillbirth, ectopic pregnancy, and fetal malformation.
15. Higher incidence of multiple pregnancies
In vitro fertilization-embryo transfer has a significantly higher rate of multiple pregnancies, which are prone to pregnancy problems such as hyperemesis, premature rupture of membranes, anemia, postpartum hemorrhage, delivery difficulties, miscarriage, preterm delivery, stillbirth, and abnormal fetal development. According to the relevant documents of the Ministry of Health, in case of multiple pregnancies with more than 2 fetuses, reduction of fetus is required. There are risks of infection, bleeding, miscarriage, premature delivery, premature rupture of membranes and fetal death, and there is no guarantee that the fetus left behind will not be deformed. The cost of reduction includes hospitalization, examination, reduction surgery and medication, etc.
16.Distant complications
Some researchers have suspected that the use of ovulation-promoting drugs increases the incidence of ovarian cancer, but the results are still inconclusive and further studies are needed.