Problem
To investigate changes in the ratio of T‐cell subpopulations expressing intracellular T helper1 (Th1) and T helper 2 (Th2) cytokines in women with a history of recurrent failed implantation under going in‐vitro fertilization (IVF)‐embryo transfer.
Method of study
Twenty‐eight peripheral blood samples were obtained at two time points, from 14 women undergoing IVF treatment; eight women with a history of recurrent failed implantation, who did not get pregnant in the index IVF cycle and six who had one or more previous successful IVF pregnancy and who became pregnant in the index IVF cycle. The proportion of lymphocytes expressing interferon‐gamma (IFN‐γ), tumour necrosis factor‐alpha (TNF‐α), and interleukin 4 (IL‐4) and the Th1:Th2 ratios of IFN‐γ:IL‐4, and TNF‐α:IL‐4 in T helper cells was measured by flow cytometry, in samples obtained before commencing IVF treatment and in samples obtained after ovarian stimulation (on the day of oocyte retrieval).
Results
In samples collected during oocyte retrieval, women with a history of recurrent failed implantation had a higher IFN‐γ:IL‐4 and TNF‐α:IL‐4 ratio than the control group, (18.6 ± 9.3 versus 6.47 ± 1.68, P = 0.009) and (39.1 ± 15.7 versus 11.53 ± 3.76, P = 0.001) respectively. In women with a history of recurrent failed implantation the ratio of IFN‐γ:IL‐4 and TNF‐α:IL‐4 at oocyte retrieval was higher than pre‐treatment ratios (18.6 ± 9.3 versus 12.01 ± 9.8, P = 0.018) and 39.10 ± 15.7 versus 18.66 ± 11.42, P = 0.010) respectively, showing a Th1 bias. In women with a successful IVF the converse was true; the ratio at oocyte retrieval was significantly lower than pre‐treatment ratios (6.47 ± 1.68 versus 9.37 ± 6.8, P = 0.035) and 11.53 ± 3.76 versus 18.60 ± 12.9, P = 0.027) respectively, representing a Th2 bias.
Conclusion
Women with a history of unexplained recurrent failed IVF treatment have a Th1 bias and this polarization is more enhanced following hormonal manipulations during IVF treatment. Comparing pre‐treatment ratios of IFN‐γ:IL‐4 and TNF‐α:IL‐4 to ratios obtained at oocyte retrieval may be clinically useful. Women with recurrent failed IVF have increasing ratios.
Internal to external iliac vessel anastomoses are an acceptable surgical technique that should be applied in a human model to ensure adequate subsequent uterine perfusion.
The study demonstrates a keen interest in UTx, partly because other options seem difficult to access. It is worth noting that people appear to be distancing themselves from the risk. This requires careful assessment in any clinical program. This study is the first to demonstrate a qualitative relationship between patients with AUFI and their curiosity and desire for UTx. It paves the way for forming the introduction into the psychological assessment of a potential patient.
A Case of Pregnancy following Allogeneic Uterine Transplantation in a Rabbit ModelPopulation 18 New Zealand white allogeneic rabbit does of proven fertility were used as donor and recipient animals (nine donors, nine recipients).
MethodsNine allogeneic UTn in the rabbit model were performed using a pre-determined protocol. Embryos were transferred into each cornua via a mini-midline laparotomy. The pregnancy was monitored with regular reproductive profiles and a colour Doppler ultrasound to measure fetal growth.
Main Outcome MeasuresPresence of conceptus, size and growth of fetus, markers of acute rejection, biochemical reproductive, renal and hepatic profiles.
ResultsRecipient #5 was the sole surviving doe out of the cohort of nine. Day 5 post-embryo transfer (D5) scan did not demonstrate a fetal sac. Fetal sac diameter on D9, D13, D16 and D18 was (mm): 17.3x13. 1, 22.1x19.5, 25.2x22.7, and 10.2x6.3. Crown-rump length was only recordable on D9, D13 and D16. Subsequent scans on D22 and D25 did not demonstrate a fetal sac, which together with the fetal sac diameter was suggestive of resorption. The recipient was sacrificed on D27.Necropsy and histopathology confirmed evidence of a gravid uterus and presence of a gestational sac.Conclusions Despite the end result of the experiment i.e. termination of pregnancy as a result of miscarriage, the study represents only the third example of conception and pregnancy following an allogeneic UTn.
Key WordsFertility, Uterine Transplantation, Rabbit, Pregnancy
Abstract Word Count 254Manucript Word Count 4414 4
The study had 528 participants. With respect to overall support for uterine transplant and as a possible future therapeutic option for absolute uterine factor infertility, 93.8% (n=495) thought that uterine transplant should take place if considered appropriate medically, surgically, and ethically and 57.2% (n=302) thought it was an achievable objective. Issues related to immunology of uterine transplant and pregnancy after uterine transplant were unanimously thought of as most important. More effort is required to educate health care professionals about all aspects of uterine transplant.
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