Meen-Yau Thum

Serial estimation of Th1:th2 cytokines profile in women undergoing in-vitro fertilization-embryo transfer.

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.

ORIGINAL ARTICLE: Prednisolone Suppresses NK Cell Cytotoxicity In Vitro in Women With a History of Infertility and Elevated NK Cell Cytotoxicity

To evaluate the effect of prednisolone on NK cell cytotoxicity in vitro environment and also to compare the effect of prednisolone versus immunoglobulin‐G (IVIG) on NK cell cytotoxicity using in vitro co‐culture with K562 cells.

The basis and value of currently used immunomodulatory therapies in recurrent miscarriage

Recurrent miscarriage (RM) without an obvious identifiable cause may arise from excessive maternal T and natural killer (NK) cell activity against the trophoblast or early embryo. Impaired regulatory T cell function leading to increased pro-inflammatory Th17 and NK cell cytotoxicity may be central. Ongoing subclinical endometrial infection and/or inflammation with increased secretion of TNFα and stimulation of autoimmunity to heat shock proteins may also be contributory. Therapies with a varying theoretical basis and clinical evidence aimed at reducing excessive endometrial immune activity have been used non-selectively in women with RM with variable success. Recent work has now improved our understanding of the role of the different immune cells and proteins that are important at each stage of a normal pregnancy. The vulnerability of the early embryo to T and NK cell-mediated rejection suggests that immune-based therapies need to be maximally effective during early pregnancy. Targeting RM women with demonstrable T and NK cell activity may improve the overall clinical efficacy of these treatments. It may also prevent costly and possibly harmful use in women who are unlikely to respond, and make better use of scarce resources. This report describes the underlying principles behind the use of the different immune-based therapies. The broad evidence supporting their efficacy is also described, as are the possible adverse consequences. Suggestions are also made on how the maternal immune system may be positively modulated using current, widely available treatments that have minimal or no side effects.

Reducing multiple pregnancy in assisted reproduction technology: towards a policy of single blastocyst transfer in younger women

Objectives  To investigate the effects of single blastocyst transfer (SBT) on live birth and multiple pregnancy in women undergoing in vitro fertilisation (IVF).

Mechanism of human chorionic gonadotrophin-mediated immunomodulation in pregnancy

Human chorionic gonadotrophin (hCG) is released within hours of fertilization and has a profound ability to downregulate maternal cellular immunity against trophoblastic paternal antigens. It also promotes angiogenic activity of the extravillous trophoblast, and impairment of this function may lead to inadequate placentation and an increased risk of preeclampsia. There is increasing evidence that hCG alters the activity of dendritic cells via an upregulation of indoleamine 2,3-dioxygenase activity. This reduces T-cell activation and cytokine production, as well as encouraging Treg cell recruitment to the fetal–maternal interface. These changes are critical in promoting maternal tolerance. hCG is also able to increase the proliferation of uterine natural killer cells, while reducing the activity of cytotoxic peripheral blood natural killer cells. There are rare reports of autoantibodies directed against hCG or the luteinizing hormone/hCG receptor in women with recurrent miscarriage. These autoantibodies are more frequent in women with thyroid autoimmunity. This may explain the association between thyroid autoimmunity and impaired fertility. Downregulating these anti-hCG and anti-luteinizing hormone/hCG receptor autoantibodies may be helpful in some women with early miscarriage or recurrent failed in vitro fertilization.

In the era of micro-dissection sperm retrieval (m-TESE) is an isolated testicular biopsy necessary in the management of men with non-obstructive azoospermia?

Study Type – Therapy (case series)

Recurrent miscarriage and autoimmunity

Both organ-specific and systemic autoimmunity are associated with an increased prevalence of recurrent miscarriage (RM). The precise mechanism for this is unclear, as cross-reactivity between trophoblastic and maternal host autoantigens has not been demonstrated. In the antiphospholipid antibody syndrome, prothrombotic mechanisms are evident, along with direct inhibitory actions against trophoblastic activity. In many types of both systemic and organ-specific immunity, however, a disturbed T-helper cell profile is seen. This is also evident in women with RM. In both cases, reduced numbers of T regulatory cells have been reported. These are required to regulate excessive activity of the Th1 and the proinflammatory Th17 subsets that, when operating through excessive natural killer cell activity, may have antipregnancy effects. Checking for underlying autoimmunity is therefore a critical analysis in women with RM and future therapies will probably be aimed at correcting the deficiency of regulatory T cells or correcting excessive Th1 and Th17 function.

Investigating psychosocial attitudes, motivations and experiences of oocyte donors, recipients and egg sharers: a systematic review

INTRODUCTION The donation of oocytes has been made feasible as a result of in vitro fertilization (IVF). This treatment offers an answer for infertile women with ovarian conditions, such as primary ovarian insufficiency. Demand for oocyte donors has been on the rise globally, with infertile couples, as well as gay men, increasingly using it as a means to found their families. With an acute shortage of oocyte donors globally, the psychosocial aspects behind oocyte donation are important for fertility clinics to understand. This paper aims primarily to provide an up-to-date systematic review of the psychosocial aspects of oocyte donation from the point of view of oocyte donors and recipients and egg sharers. Its secondary aims are to explore the motives and experiences of donors as well as attitudes towards donor anonymity and disclosure. An emphasis has been placed on the analysis of donors in the UK. No review has analysed together the aforementioned donor groups along with recipient group. METHODS A systematic search of English peer-reviewed journals of four computerized databases was undertaken, with no time restriction set for publications. RESULTS There were 62 studies which met the inclusion criteria and were included in the systematic review. Attitudes towards donation were positive from both a donor oocyte and recipient point of view, with medical procedures being well tolerated and excellent post-donation satisfaction among all donor groups. There were distinct differences between the different donor groups and recipients in motivation for oocyte donation and decisions for disclosure. Attitudes towards anonymity issues were reassuring with a significant proportion of donors of all types willing to donate as identifiable donors. However, there were methodological limitations identified in the studies reviewed. CONCLUSION This review successfully explored the important psychosocial aspects of oocyte donation. In general terms the attitudes and feeling of patients involved from all sides of the donation process were extremely positive. A number of key and consistent issues emerged which demonstrated differences and similarities between the different donor groups, as well as a greater understanding of the recipient. With regard to psychosocial well-being, the results were reassuring throughout all donor groups, especially the egg share donors. Although it seems the 2005 legislative changes in the UK have not caused the anticipated dramatic decrease in gamete donation, oocyte donation still falls far short of demand. The UK has an increasing population of patients from different ethnic backgrounds and same sex relationships seeking oocyte donation, with very few studies including these groups of patients. An increased number of well-designed studies looking into the psychological issues surrounding gamete donation of different patient groups, could allow more directed assessment and counselling of oocyte donors and recipients, with a resulting increase in donor recruitment.

Uterine allotransplantation in a rabbit model using aorto-caval anastomosis: a long-term viability study

OBJECTIVE Uterine transplantation (UTx) has been proposed as a treatment option for women diagnosed with absolute uterine factor infertility. Allogeneic UTx has been attempted in a number of animal models, but achieving an adequate blood supply for the transplanted uterus still presents the biggest challenge. Microvascular re-anastomosis was unsuccessful in a number of animal models. The aim was to assess whether a large vessel aortic-caval vascular patch technique can bring about long-term graft survival after allogeneic UTx in a rabbit model. STUDY DESIGN A longitudinal study involving uterine cross transplantations (n=9 donors, n=9 recipients) was performed in New Zealand white rabbits using an aortic-caval macrovascular patch harvested as part of the uterine allograft. All rabbits were allogeneic and of proven fertility, with at least one previous litter each. The end result of the donor graft harvest was a total hysterectomy transecting across the vagina and the most lateral aspects of the uterine horns together with an aortic-caval macrovascular patch (aorta, inferior vena cava, common and internal iliacs, and uterine arterial and venous tree). Tacrolimus (500 μg twice daily) was administered for immunosuppression post-transplant. The recipients were closely monitored until death or euthanasia. RESULTS In this case series, long-term rabbit survival was 11% (n=1). Surgical survival was 56% (n=5). Three rabbits (UTx #3, #4 and #8) died intra-operatively as a result of blood aspiration, ventricular hematoma, and massive hemorrhage. Three does (#1, #2, #7 and #9) died within the first 24 h as a result of the veno-vena and anastomosis breakdown. Does #6 and #9 died secondary to pre-operative pneumonia and a pulmonary embolus, respectively. Only one rabbit survived longer than a month. CONCLUSION Our method used a macrovascular patch technique to ensure adequate blood supply to the donor uterine graft. We have demonstrated the feasibility of uterine allotransplantation using this technique in the rabbit, but were unable to demonstrate a higher long-term survival percentage because of issues related to using a rabbit model.

Multispectral imaging of organ viability during uterine transplantation surgery in rabbits and sheep

Abstract. Uterine transplantation surgery (UTx) has been proposed as a treatment for permanent absolute uterine factor infertility (AUFI) in the case of the congenital absence or surgical removal of the uterus. Successful surgical attachment of the organ and its associated vasculature is essential for the organ’s reperfusion and long-term viability. Spectral imaging techniques have demonstrated the potential for the measurement of hemodynamics in medical applications. These involve the measurement of reflectance spectra by acquiring images of the tissue in different wavebands. Measures of tissue constituents at each pixel can then be extracted from these spectra through modeling of the light–tissue interaction. A multispectral imaging (MSI) laparoscope was used in sheep and rabbit UTx models to study short- and long-term changes in oxygen saturation following surgery. The whole organ was imaged in the donor and recipient animals in parallel with point measurements from a pulse oximeter. Imaging results confirmed the re-establishment of adequate perfusion in the transplanted organ after surgery. Cornual oxygenation trends measured with MSI are consistent with pulse oximeter readings, showing decreased StO2 immediately after anastomosis of the blood vessels. Long-term results show recovery of StO2 to preoperative levels.