Embryo Implantation
April 1, 2017
By John C. Hobbins, MD
Professor, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora
Dr. Hobbins reports no financial relationships relevant to this field of study.
SYNOPSIS: A recent study tracking embryos after embryo transfer has provided insight into why embryos have a greater tendency to ultimately implant in the lower uterine segment, thereby predisposing patients to a greater risk of placental complications.
SOURCE: Saravelos SH, Wong AW, Chan CP, et al. How often does the embryo implant at the location to which it was transferred? Ultrasound Obstet Gynecol 2016;48:106-112.
Have you wondered why patients using some forms of assisted reproductive technology (ART) have higher rates of placenta-related complications? A group from Hong Kong recently published information to explain why this may happen. The study was designed to track the location of an embryo from the time of transfer to its ultimate residence in the uterus at three weeks post-transfer.
Patients having embryo transfer (ET) were studied with 2-D and 3-D ultrasound examinations during the time of transfer, one minute later, and 60 minutes after ET. The last 3-D exam was conducted three weeks post-ET. An attempt was made to place three-day-old embryos into the middle portion of the uterus (10-20 mm from the fundus) under ultrasound guidance. The embryos were accompanied by a tiny amount of air, and the location of the embryo was determined by the presence of bright echoes (representing the air bubbles) at one minute and 60 minutes. In addition, the investigators assessed the presence, frequency, and direction of uterine contractions at these same time intervals using three-minute ultrasound real-time clips. The frequencies of contractions were classified as “high” (> 2 per minute) or “low” (< 2 per minute). Last, at three weeks’ gestation the final location of the implanted embryo was determined with 3-D ultrasound using planar reconstruction.
Over the study period, 239 patients had ET procedures and 46% became pregnant, 71 of whom had adequate ultrasound information provided by the four ultrasound evaluations. The embryo location at three weeks was found to coincide with the bubble site in 29/71 (40.8%) at one minute and in 36/71 (50.7%) at 60 minutes. At 60 minutes, there was an 85% chance of the embryo staying at that original site if it was in the lower uterine segment. Those in the upper segments were more likely to move.
The contraction data were fascinating. Surprisingly, the direction of uterine contractions was not related to the ultimate implantation site, nor was the frequency of contractions at one minute related. However, a high frequency of contractions at 60 minutes was associated with a twofold increase in the chance of low implantation.
COMMENTARY
Why are we discussing a fertility paper in the obstetrical section of OB/GYN Clinical Alert? Because this well-constructed paper may answer important questions regarding why patients conceiving through ART are so much more prone to problems related to the placenta. Also, it can be a catalyst to a discussion of the obstetrical management of women who used ART.
The Saravelos et al study indicates that no matter how carefully one would avoid inserting an embryo into the lower uterine cavity, these embryos seem to have a higher tendency than spontaneously conceived embryos to alight in the lower uterine segment — and it may be due to increased uterine contractions at the time of, and/or shortly after, the procedure, driving the embryos downward.
Low embryo implantation begets low placental implantation. Patients undergoing in vitro fertilization (IVF) have a greater chance of placenta previa,1 as well as accreta,2 and a 10-fold increased risk of vasa previa.3 They also have a greater chance of small for gestational age fetuses4 and preeclampsia,5 which may be due to the quality of placentation rather than the position of the placenta. Although maternal age is a factor, and more patients using ART are of advanced maternal age (AMA), the relationship between preeclampsia and ART seems to be even stronger than with age alone. The obvious relationship between ART and multiple gestations is worth a separate article, as is the increased risk of fetal anomalies.
Below are suggestions for managing patients after ET:
- Whether or not the patient is AMA, a nuchal translucency (NT) exam is helpful at 10/6 weeks to 13/6 weeks, since fetuses with increased NTs are more likely to have cardiac abnormalities.
- An anatomy scan at 18-20 weeks and an assessment of placental position are useful because of the higher risk for placenta previa. The placenta should be investigated for early signs of accreta, especially if the placenta is over an old cesarean scar. Except for the fetal heart, most fetal anomalies that have been linked to ART can be identified at this time.
- During the above anatomy scan at 20 weeks, the cord insertion site always should be determined since vasa previa involving the cord always is velamentous. Also, the presence of an accessory lobe should be ruled out, since connecting vessels occasionally stray over the cervix.
- A second trimester alpha-fetoprotein test can be useful, since more than 50% of patients with accreta will have very high levels of this fetal product.6
- With IVF, some have recommended that a fetal echocardiogram be accomplished at 22 weeks since there is an increased rate of tetralogy of Fallot,7 which on occasion can escape detection during an 18-week sonogram.
- Another examination at 30 weeks is useful to track fetal growth and to look again for signs of accreta or the later development of vasa previa secondary to atrophy of placental tissue near the cervix.
REFERENCES
- Romundstad LB, Romundstad PR, Sunde A, et al. Increased risk of placenta previa in pregnancies following IVF/ICS I; a comparison of ART and non-ART pregnancies in the same mother. Hum Reprod 2006;21:2353-2358.
- Kaser DJ, Melamed A, Bormann CL, et al. Cryopreserved embryo transfer is an independent risk factor or placenta accreta. Fert Steril 2015;103:1176-1184.
- Schachter M, Tovbin Y, Arieli S, et al. In vitro fertilization is a risk factor for vasa previa. Fertil Steril 2002;78:642-643.
- Cooper AR, O’Neill KE, Allsworth JE, et al. Smaller fetal size in singletons after infertility therapies: The influence of technology in the underlying infertility. Fert Steril 2012;96:1100-1106.
- Tandberg A, Klungsoyr K, Romundstad LB, Skjaerven R. Pre-eclampsia and assisted reproductive technologies: Consequences of advanced maternal age, interbirth intervals, new partner and smoking habits. BJOG 2015;122:915-922.
- Gagnon A, Wilson RD, Audibert F, et al. Obstetrical complications associated with abnormal serum marker analytes. J Obstet Gynaecol Can 2008;30:918-929.
- Tararbit K, Lelong N, Thieulin AC, et al. The risk of four specific congenital heart defects associated with assisted reproductive techniques: A population-based evaluation. Hum Reprod 2013;28:367-374.
A recent study tracking embryos after embryo transfer has provided insight into why embryos have a greater tendency to ultimately implant in the lower uterine segment, thereby predisposing patients to a greater risk of placental complications.
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