Risks to women and babies associated with IVF

As with all medical treatments, even in IVF there are some risks. Although complications are reported to occur infrequently, counselling of patients on possible complications of IVF treatment is necessary before informed consent can be obtained. The drugs used for ovarian stimulation have very mild side effects for some women including soreness at the injection site, headaches and mood swings.  However it is possible to identify some complications

ovarian hyperstimulation syndrome (OHSS.) OHSS is one of the  most iatrogenic complication associated with ovarian stimulation. This syndrome involves alterations of the fluid and electrolyte balance and of blood coagulation and is associated with an abnormal increase in ovary volume, ascites and pleural effusion, the possible onset of thromboembolic events and various other complications. The literature reports an incidence of ovarian hyperstimulation syndrome of 0.5% to 2%. There are anyway a number of strategies to minimise the risk of OHSS.  Primary prevention in reducing the risk of OHSS includes personalized stimulation protocol in order to adjust patient’s characteristics (Antral Follicular Count, AMH).

If the risk of developing this condition is high, the doctors at the Center may decide: – to suspend the cycle – to cryopreserve oocytes – or, in the cases of post-fertilization onset, not to carry out the transfer of embryos and proceed with their cryopreservation and deferred transfer as soon as health conditions allow it, as provided for by the law (Article 14, paragraph 3), to be implemented as soon as possible.

However the literature strongly support that the induction of final oocyte maturation with a bolus of gonadotropin-releasing hormone (GnRH) agonist (GnRHa), instead of the criterion standard hCG, in patients undergoing ovarian stimulation significantly reduces the risk of OHSS and could be considered to  mandatory when we suspect excessive ovarian response. The GnRH agonist trigger with freeze all approach  (oocytes or embryos) and ET in a subsequent unstimulated cycle is considered an efficient way to reduce risk of OHSS. (secondary prevention). This approach is possible only with an efficient  cryopreservation program .

– Adnexal torsion is an infrequent but serious complication of ovarian stimulation and should be considered in every patient with complaints of abdominal pain and nausea during or after ovarian stimulation.

– Complications after transvaginal ultrasound-guided follicle aspiration are infrequent but potentially serious: pelvic visceral, vascular injuries (0,04%) and abdominal bleeding (0,07) have been reported. PID is another potential hazard after oocyte retrieval. However the possibility of infectious complications arising from intra-uterine transfer of embryos, though never reported in the literature, cannot be ruled out. If oocyte retrieval is done under anaesthesia, it implies the risks typical of the anaesthesia procedure adopted.

Ectopic pregnancy (EP) is a form of abnormal pregnancy in which the embryo implants outside the intrauterine cavity and it is one of the major event in a woman’s reproductive life. EP is the leading cause of maternal morbidity during the first trimester and the incidence occurring in approximately between 0.5 and 3 % depending on whether a tube-related factor of infertility is present.

– There is also the possibility (1% to 10% depending on the number of follicles obtained) that retrieval may result in a failure to collect oocytes or in collecting only immature or post-mature oocytes that are not usable for insemination.

– Transfer to the uterus of more than one embryo exposes the patient to the risk of multiple pregnancy (twins or triplets), with an increased risk of diseases during pregnancy (preterm birth, premature rupture of membranes, diabetes, hypertension, preclampsia) and the necessity of resorting almost always to a C-section.

Pursuant to the current law on medically assisted procreation, selective embryo reduction of multiple pregnancies is forbidden except in the cases provided for by Law No. 194 of 22 May 1978.

– Finaly, the incidence of miscarriage overlaps with that in the case of natural conception.


Possible risks for the unborn child


The assessment of the risk of abnormalities, malformations, and neonatal pathologies is very difficult and presents several problems in the analysis of the data, such as maternal age higher than the average of the population and the possible presence of genetic factors linked to infertility.

According to the most recent and extensive data available in the literature with regard to the cases analysed, the risk of malformations is slightly higher in children born from assisted procreation. In particular, a prospective study published in 2004 reported a percentage of malformations of 6.1% in children conceived spontaneously and of 8.7% in those conceived following IVF-ET or ICSI (Fertil Steril 2004). More recently, an extensive case-control study showed a slightly higher percentage of malformations in children born from IVF-ICSI compared to those spontaneously conceived (11.0% vs 5.6%), but this difference is not statistically significant (p = 0.099) (Ann Pediatric 2009). A large-scale study carried out on the most recent data in the literature shows that the family background is even more important than the technique with regard to increased risk of congenital malformations in children born from medically assisted procreation techniques (Placenta 2008). Children born from ICSI due to severe male factor infertility have an increased risk of chromosomal abnormalities (de novo: 1.6% versus 0.5%; transmitted: 1.4% versus 0.4% of the normal population). The increase seems to be correlated more to the altered quality in semen parameters than to the ICSI technique itself (Hum Reprod 2002). However, there seem to be no statistically significant differences with regard to the presence of possible neonatal pathology in children born with ICSI using fresh spermatozoa from ejaculation or by surgical retrieval (Fertl Ster 2011). In addition, analysing the difference between the percentage of malformations in children born from fresh cycle or frozen cycle by IVF-ET/ICSI, most of the literature agrees that in this case as well there are no statistically significant differences between the two study groups (Wennerholm, Hum Reprod 2011).

Finally, the data relating to the cognitive and psychomotor development show no difference between the children conceived spontaneously or following IVF-ET and ICSI (Hum Reprod 2003, Hum Reprod Up 2008). These data were confirmed by a recent study that assessed their ability to socialize compared to children conceived spontaneously in addition to these two aspects (Neuropediatrics, 2011).