Reduced risk of "small for gestational age baby" following frozen embryo transfer in endometriosis patients

Pregnancy-related complications including small for gestational age are encountered more frequently in both patients with endometriosis and patients receiving assisted reproductive technology treatment.

Key Points

Highlights:

• Infertile patients having endometriosis with frozen embryo transfer due to the reduced risk of perinatal complications, especially small for gestational age.  

Importance:

• Women who will be managed with assisted reproductive technology treatment should be counseled about the obstetric and perinatal complications such as small for gestational age, hypertensive disorders of pregnancy, antepartum hemorrhage, intrauterine death, preterm delivery.

What’s done here?

• This observational cohort study was conducted in endometriosis patients having singleton pregnancies after assisted reproductive technology treatment at a university-based reproductive center.
• Endometriosis-associated infertility patients younger than 43years; received in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), and achieving singleton pregnancy were included.
• Vaginal progesterone and transdermal/oral estrogen supplementation were prescribed in fresh cycles and were recommended in frozen-thawed cycles.
• The primary outcome was small for gestational age (birth weight below 10th percentile).
• Secondary outcomes were pregnancy outcomes (late miscarriage, congenital anomalies, hypertensive pregnancy disorder, gestational diabetes, antepartum hemorrhage, preterm membrane rupture, intrauterine death), perinatal outcomes (preterm delivery, gender, birth weight, large for gestational age, Apgar, admission to NICU, perinatal mortality).
• The demographic and clinical characteristics, obstetric and perinatal outcomes were compared between fresh and frozen embryo transfer in the patients with endometriosis.

Key results:

• A total of 339 patients who met the eligibility criteria were included. Fresh embryo transfer (112 patients) and frozen embryo transfer (227 patients) compared.
• The demographic and clinical characteristics of the patients and the phenotypes of endometriosis did not show any significant difference between the groups.
• There was a significant difference regarding the history of prior surgery for endometriosis (43.8% vs 30.8% in fresh and frozen cycles, respectively) and the presence of coexistent adenomyosis (48% vs 32.1% in fresh and frozen cycles, respectively).
• The patients in frozen embryo transfer were found to have a reduced risk of "small for gestational age". 

Strengths and Limitations

• This is the first study to compare the risk of obstetric and perinatal outcomes between the fresh and frozen cycles in patients with endometriosis-associated infertility.
• The methodological design, large sample size, and well-defined endometriosis phenotypes were strengths.
• The inclusion of the patients without histopathologically-proven endometriosis could be accepted as the limitation of the study. The cohort design, rather than a randomized trial, was another limitation. Thus, multivariable analysis was performed to exclude the effect of potential confounders. Prenatal genetic tests were not performed at the study center to diagnose chromosomal abnormalities which could influence the risk of small for gestational age.

Lay Summary

Infertility is encountered frequently in patients with endometriosis. These women could be managed using assisted reproductive technology (ART) including in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) to achieve pregnancy.

However, some adverse obstetric and perinatal outcomes are experienced more commonly in these pregnancies due to the intrinsic and/or extrinsic characteristics of the patients. Ovarian stimulation protocols, laboratory techniques, type of embryo transfer, altered implantation and subsequent placental function, local disturbances during the embryo transfer, hormonal stimulation on the endometrium, and the disease itself influence the risk of obstetric and perinatal outcomes. "Small for gestational age" baby is one of these adverse outcomes, which is defined as birth weight below the 10th percentile.

Bourdon et al, a group of researchers from France, published a study titled “Risk of small for gestational age is reduced after frozen compared with fresh embryo transfer in endometriosis” in the journal "Reproductive BioMedicine Online". The authors sought to compare the risk of small for gestational age and other obstetric and perinatal outcomes between fresh and frozen embryo transfer in the patients with endometriosis-associated infertility.

They included the patients having endometriosis which was diagnosed according to imaging modalities or histopathological proof in the previous surgery. They also compared all demographic and clinical variables of the patients and found no significant difference. There was a significant difference regarding the history of prior surgery for endometriosis (more frequently in fresh cycles) and the presence of coexistent adenomyosis (more frequently in fresh cycles). Although the risks of obstetric and perinatal outcomes were similar between the fresh and frozen cycles, the risk of "small for gestational age baby" was reduced significantly after adjusting potential confounding factors.

“Frozen embryo transfer may be a safe option in terms of fetal birth weight in endometriosis-affected women” the authors added.

Research Source: https://pubmed.ncbi.nlm.nih.gov/33077356/