To study the effects of gamma irradiation on single donor apheresis platelet units by measurement of cellular counts,functional indicators and a panel of biochemical parameters,in order to assess pre-transfusion platelet quantity and quality during the shelf life of the product

Background

The occurrence of transfusion associated graft versus host disease can be prevented by gamma irradiation of blood components. This study was undertaken to assess the effects of gamma irradiation on single donor platelet (SDP) concentrate units.

Method

SDPs were collected by a continuous flow apheresis technique (n = 400). The SDPs from each donor were divided into two parts, one gamma-irradiated with 25 Gy and the other used as a non-irradiated control. Swirling and morphological features, cellular counts, biochemical parameters including blood gas analysis, and platelet activation levels (CD62P: p-selectin) by flow cytometry were analyzed on Day 1 and on Day 5.

Results

Swirling and morphology were maintained in all products, in both the groups throughout the shelf life. No significant change was seen in both groups, on the first and fifth day, as far as pO₂, pCO₂, Na⁺, K⁺, HCO₃⁻ & Ca²⁺ were concerned. However, lactate increased and glucose decreased significantly in irradiated products over 5-day storage period. A small but significant decrease in pH and platelet count was found in the irradiated PCs after 5-day storage. The mean proportion of platelets expressing CD62P over 5-day storage increased significantly.

Conclusion

After an overall assessment of all our in vitro parameter results and observations, a few of which were significant, while most were not significant, we concluded that a well-preserved quality of gamma irradiated apheresis platelets is maintained throughout the entire 5-day shelf life of the platelet product, with minimal difference compared to non-irradiated platelets.     

Platelet kinetics after slow versus standard transfusions: a pilot study

Background

Platelet transfusion is required in the acute phase of some thrombocytopenic disorders in order to prevent potentially dangerous hemorrhages.The purpose of this study was to assess the increase in platelet count following a slow platelet transfusion.

Methods

Patients suffering from thrombocytopenia due to various underlying diseases were enrolled in the prospective pilot feasibility trial and were randomly divided into two groups. Standard platelet transfusion was administered in one group, while slow transfusion was used in the other. The platelet count was examined at 1 hour, 24 hours, and 1 week following the transfusions.

Results

Although the platelet count was higher following 1 hour after transfusion via the standard method, the count tended to be higher 1 week after the transfusion in the slow transfusion group. This difference, however, only turned out to be statistically significant amongst females.

Conclusion

A therapy of slow platelet transfusion might be more effective for the prevention of platelet loss. Further studies will be required to strengthen this hypothesis.     

Extracting Rx information from clinical narrative

Objective

The authors used the i2b2 Medication Extraction Challenge to evaluate their entity extraction methods, contribute to the generation of a publicly available collection of annotated clinical notes, and start developing methods for ontology-based reasoning using structured information generated from the unstructured clinical narrative.

Design

Extraction of salient features of medication orders from the text of de-identified hospital discharge summaries was addressed with a knowledge-based approach using simple rules and lookup lists. The entity recognition tool, MetaMap, was combined with dose, frequency, and duration modules specifically developed for the Challenge as well as a prototype module for reason identification.

Measurements

Evaluation metrics and corresponding results were provided by the Challenge organizers.

Results

The results indicate that robust rule-based tools achieve satisfactory results in extraction of simple elements of medication orders, but more sophisticated methods are needed for identification of reasons for the orders and durations.

Limitations

Owing to the time constraints and nature of the Challenge, some obvious follow-on analysis has not been completed yet.

Conclusions

The authors plan to integrate the new modules with MetaMap to enhance its accuracy. This integration effort will provide guidance in retargeting existing tools for better processing of clinical text.     

A Comparative Study of Laparoscopic with Conventional Open Donor Nephrectomy in Renal Transplantation

Background

Laparoscopic donor nephrectomy (LDN) has been gaining popularity among kidney donors. There have been concerns about the safety and efficacy of the procedure as compared to open donor nephrectomy (ODN). We compare our results on LDN with ODN.

Methods

We retrospectively analysed our data of LDN and ODN. Duration of surgery, blood loss, period of hospitalisation, per oral intake and analgesic requirements.

Result

22 LDNs were done, the operation time ranged from 220-300 minutes, and blood loss from 100-150ml. In the first 10 laparoscopic operations four cases required conversion to open surgical dissection. Only one case was converted to open surgery in the subsequent 12 laparoscopic cases. Oral intake was started on the first postoperative day. Analgesic requirement in laparoscopy cases was less. Patients were mobilised on the first day after surgery. Patients were discharged by seventh day. There was no significant difference in the functioning of the graft after revascularisation in the recipient.

Conclusion

Laparoscopic donor nephrectomy is a safe and effective technique of donor nephrectomy.Key Words: Laparoscopy, Laparoscopic donor nephrectomy, Living kidney donors, Kidney transplantation     

Seasonal variation of platelets in a cohort of Italian blood donors: a preliminary report

Background

Since available data are not univocal, the aim of this study was to explore the existence of a seasonal variation in platelet count.

Methods

The study was based on the database of the Italian Association of Blood Volunteers (AVIS), section of Ferrara, Italy, 2001–2010. Hematological data (170,238 exams referring to 16,422 donors) were categorized into seasonal and monthly intervals, and conventional and chronobiological analyses were applied.

Results

Platelets and plateletcrit were significantly higher in winter-autumn, with a main peak in December-February (average +3.4% and +4.6%, respectively, P <0.001 for both).

Conclusions

Although seasonal variations have been reported for several acute cardiovascular diseases, it is extremely unlikely that such a slight increase in platelet count in winter alone may be considered as a risk factor.     

Clinical evaluation of Deep Anterior Lamellar Keratoplasty (DALK) for stromal corneal opacities

Background

Corneal scars are commonly formed following many diseases of the eye like trauma, inflammation and infections. They lead to permanent diminution of vision which can be managed by Penetrating Keratoplasty (PK). PK is removing diseased as well as healthy tissues and is associated with many post-operative complications. Deep Anterior Lamellar Keratoplasty (DALK) is a relatively newer procedure which replaces only the diseased stroma, leaving the original corneal endothelium intact. This procedure is associated with lesser incidence of post-operative complications.

Methods

The study was conducted at a large tertiary care centre. 10 patients with stromal corneal scars were subjected to DALK and results were analysed after 06 months. Poor quality donor corneal tissue of B− and C grade was used in all cases.

Results

7 out of 10 patients (70%) undergoing DALK had post-operative visual acuity of 6/24 or better. 03 patients who did not have adequate recovery of visual acuity were due to over-riding of the graft in 01 case (10%), fungal keratitis in 01 case (10%) and interface haze in 01 case (10%).

Conclusion

DALK is a promising new technique for management of superficial corneal stromal scars using poor quality donor corneal tissue. Initial results are encouraging with minimal complications.     

A sequence labeling approach to link medications and their attributes in clinical notes and clinical trial announcements for information extraction

Objective

The goal of this work was to evaluate machine learning methods, binary classification and sequence labeling, for medication–attribute linkage detection in two clinical corpora.

Data and methods

We double annotated 3000 clinical trial announcements (CTA) and 1655 clinical notes (CN) for medication named entities and their attributes. A binary support vector machine (SVM) classification method with parsimonious feature sets, and a conditional random fields (CRF)-based multi-layered sequence labeling (MLSL) model were proposed to identify the linkages between the entities and their corresponding attributes. We evaluated the system''s performance against the human-generated gold standard.

Results

The experiments showed that the two machine learning approaches performed statistically significantly better than the baseline rule-based approach. The binary SVM classification achieved 0.94 F-measure with individual tokens as features. The SVM model trained on a parsimonious feature set achieved 0.81 F-measure for CN and 0.87 for CTA. The CRF MLSL method achieved 0.80 F-measure on both corpora.

Discussion and conclusions

We compared the novel MLSL method with a binary classification and a rule-based method. The MLSL method performed statistically significantly better than the rule-based method. However, the SVM-based binary classification method was statistically significantly better than the MLSL method for both the CTA and CN corpora. Using parsimonious feature sets both the SVM-based binary classification and CRF-based MLSL methods achieved high performance in detecting medication name and attribute linkages in CTA and CN.     

Platelet Functions in Cardiopulmonary Bypass Surgery

Background

Haemorrhage after Cardio Pulmonary Bypass (CPB) Surgery is a well recognised complication that leads to significant morbidity and mortality. The incidence varies between 5-25% depending upon the clinical situation. Several factors are implicated as causative but none have been precisely proved.

Methods

Our study was an attempt to evaluate the haemostatic defect with particular reference to platelet function abnormalities during cardio pulmonary bypass surgery, in order to reduce the morbidity and mortality associated with post CPB haemorrhage. Flow cytometric evaluation of different platelet glycoproteins like GPIb/IX, GPIIb/IIIa and GMP-140 was done.

Results

The marker expression showed deregulation during surgery which returned to base after bypass was terminated. In contrast, the cases with bleeding showed significant variation. P-Selectin (GMP 140) expression decreased progressively till 3^rd post-operative day showing lack of activation of platelets in cases of severe bleeding.

Conclusion

Longer duration of CPB initiates plasmin generation through heparin, which raises the PAI-1-tPA complex and thereby down regulating the functions of platelets. This suggests a link between duration of CPB, bleeding, platelet dysfunction and fibrinolysis. Hence serial estimations of the levels of GMP-140 and tPA can predict severe bleeding.Key Words: CardioPulmonary Bypass, Platelet dysfunction, flowcytometry, platelet glycoproteins, haemorrhage     

Impact of platelet count on results obtained from multiple electrode platelet aggregometry (Multiplate™)

Objectives

Use of potent antiplatelet drugs requires evaluation of platelet function. While platelet function in elective cases is usually assessed in a central laboratory environment, there is also an urgent need for rapid perioperative point-of-care assessment. Recently, multiple electrode platelet aggregometry has been developed and assumed to measure platelet function independent from platelet count. We tested the hypothesis that results of multiple electrode platelet aggregometry are affected by platelet count, in particular if platelet count is below normal range.

Methods

Whole blood samples from 20 healthy volunteers were prepared containing platelet concentrations of 50,000, 100,000, 150,000, 200,000, and 250,000 μl^-1 while maintaining hematocrit. Platelet aggregation was induced by collagen, thrombin receptor activating peptide 6 (TRAP-6), adenosine-diphoshate (ADP), and arachidonic acid, respectively, and aggregation was measured by multiple electrode platelet aggregometry (Multiplate™).

Results

Results of multiple electrode platelet aggregometry significantly decreased in blood samples with platelet count below normal range. Compared to results measured in blood samples with platelet count within normal range, aggregometry results decreased by 18.4% (p < 0.001) and 37.2% (p < 0.001) in blood samples with a platelet count of 100.000 and 50.000 μl^-1, respectively. On the other hand, large interindividual variation has been observed and some blood samples showed normal results even with platelet counts of 50.000 μl^-1.

Conclusion

The results obtained with Multiplate™ Analyzer are influenced by platelet function as well as platelet count thus displaying the overall platelet aggregability within the blood sample rather than platelet function alone.     

Web 2.0 technologies for undergraduate and postgraduate medical education: an online survey

Objectives

To identify the current familiarity and use of Web 2.0 technologies by medical students and qualified medical practitioners, and to identify the barriers to its use for medical education.

Methods

A semi‐structured online questionnaire survey of 3000 medical students and 3000 qualified medical practitioners (consultants, general practitioners and doctors in training) on the British Medical Association''s membership database.

Results

All groups had high familiarity, but low use, of podcasts. Ownership of digital media players was higher among medical students. There was high familiarity, but low use, of other Web 2.0 technologies except for high use of instant messaging and social networking by medical students. All groups stated that they were interested in using Web 2.0 technologies for education but there was lack of knowledge and skills in how to use these new technologies.

Conclusions

There is an overall high awareness of a range of new Web 2.0 technologies by both medical students and qualified medical practitioners and high interest in its use for medical education. However, the potential of Web 2.0 technologies for undergraduate and postgraduate medical education will only be achieved if there is increased training in how to use this new approach.     

Comparative study of automated cryopreservation of red blood cells

Background

Strategic blood reserves are an important component in meeting blood needs and this can be accomplished through the establishment of a frozen blood program.

Methods

One hundred units of packed RBC were glycerolized using the Haemonetics ACP 215 automated cell processor and placed in a −86 °C deep freezer for freezing and storage. Product weight, hematocrit, RBC count, WBC count and hemoglobin were recorded prior to freezing. Twenty five bags were thawed and deglycerolized after every three months starting at one year from the date of first glycerolization In addition to the earlier parameters the bags were assessed for supernatant osmolality, pH, supernatant hemoglobin, ATP levels and supernatant potassium and from these red cell recovery, percentage hemolysis, supernatant glycerol and red cell viability were estimated. All tests were repeated at the end of 7 and 14 days.

Results

The mean red cell recovery was found to be 86.12% on Day 0 and 84% on Day 14. All the bags showed residual glycerol and pH within the acceptable limits upto Day 14. Percentage hemolysis, Mean ATP levels and mean supernatant potassium levels were within acceptable limits upto Day 14. All the units were sterile upto Day 14.

Conclusion

The data in this study showed that the red cells which were glycerolized using the automated platform ACP 215, frozen at −80 °C for more than a year and deglycerolized again using the ACP 215 had excellent viability while being stored at 4 °C during the 14 days of post-thaw storage.     

Perforator flap: A novel method for providing skin cover to lower limb defects

Background

Soft tissue defects in the lower limb pose a formidable challenge due to lack of reliable local flap options. Due to thin non-expendable soft tissues and predisposition to massive edema formation, even small defects become problematic. Perforator flaps represent the latest trends in soft tissue coverage. The aim of this study was to evaluate the effectiveness of perforator flaps as coverage of soft tissue defects in lower limbs.

Material and methods

A series of patients with soft tissue defects of various etiologies in the lower limb were treated using perforator flap at a tertiary care service hospital. Six were free flaps and fourteen pedicled flaps. Doppler ultrasound was used to identify recipient and donor vessels pre-operatively.

Results

Only one flap was lost due to venous congestion. In another case of carcinoma penis there was delayed healing due to persistent lymphorrhoea as a result of post-operative status following lymph node dissection and radiotherapy. Fifteen donor sites required split skin grafting, as they could not be closed directly.

Conclusion

Perforator flaps are a reliable option for closure of soft tissue defects of lower limb irrespective of size, location and depth. There is minimal donor site morbidity. It has the advantage of rapid dissection, flap elevation and reliable skin territory. As no special equipment is required it can be replicated in smaller centers also.     

Seroprevalence of human parvovirus B19 in healthy blood donors

Background

Human parvovirus B19 is an emerging transfusion transmitted infection. Although parvovirus B19 infection is connected with severe complications in some recipients, donor screening is not yet mandatory. To reduce the risk of contamination, plasma-pool screening and exclusion of highly viraemic donations are recommended. In this study the prevalence of parvovirus B19 in healthy blood donors was detected by ELISA.

Methods

A total of 1633 samples were screened for IgM and IgG antibodies against parvovirus B19 by ELISA. The initial 540 samples were screened for both IgM and IgG class antibodies and remaining 1093 samples were screened for only IgM class antibodies by ELISA.

Results

Net prevalence of IgM antibodies to human parvovirus B19 in our study was 7.53% and prevalence of IgG antibodies was 27.96%. Dual positivity (IgG and IgM) was 2.40%.

Conclusion

The seroprevalence of human parvovirus B19 among blood donor population in our study is high, and poses an adverse transfusion risk especially in high-risk group of patients who have no detectable antibodies to B19. Studies with large sample size are needed to validate these results.     

Sorafenib after combination therapy with gemcitabine plus doxorubicine in patients with sarcomatoid renal cell Carcinoma: a prospective evaluation

Background

Sarcomatoid renal cell cancer (RCC) is a distinct histological variant of RCC that is associated with rapid progression and a poor prognosis. The optimal treatment for patients with sarcomatoid RCC remains to be defined. Gemcitabine plus doxorubicine (GD) has shown some efficacy, however durability of response is limited. We carried out a prospective, open-label study to investigate the efficacy and safety of sorafenib in patients after GD failure in sarcomatoid RCC.

Methods

Fifteen patients with pure sarcomatoid RCC and objective progressive disease were treated with GD (gemcitabine 1500 mg/m², doxorubicine 50 mg/m² administered by weekly intravenous infusion) until progression of disease. Subsequently 9 patients were switched to sorafenib (400 mg twice daily). Tumor response was measured by physical examination and computerized tomography scans and evaluated according to Response Evaluation Criteria in Solid Tumors criteria.

Results

Median time to progression (TTP) under GD was 6.6 months (range 0.8 - 8 months). During GD treatment there were no remissions and 6 patients died from progressive disease. Median TTP for the 9 patients switched to sorafenib was 10.9 months (range 0.6 - 25.5 months). During sorafenib therapy one patient had a partial remission lasting for 3 months and 4 patients experienced stable disease with a duration of 3 to 9 months. Four patients immediately progressed on sorafenib treatment but had a slower dynamic of tumor progression than under GD. Dosing in both treatment phases was generally well tolerated with manageable toxicities and no requirement for dose reduction.

Conclusions

Chemotherapy with GD was ineffective in our patients with pure sarcomatoid RCC. Subsequent anti-angiogenic treatment using the multi-tyrosine kinase inhibitor sorafenib resulted in additional progression-free survival in 5 of 9 patients. Further evaluation of targeted anti-angiogenic agents for the treatment of sarcomatoid RCC is warranted.     

Use of marginal organs in kidney transplantation for marginal recipients: too close to the margins of safety?

Objective

Due to organ shortage, average waiting time for a kidney in Germany is about 4 years after start of dialysis. Number of kidney grafts recovered can only be maintained by accepting older and expanded criteria donors. The aim of this study was to analyse the impact of donor and recipient risk on kidney long-term function.

Methods

All deceased kidney transplantations were considered. We retrospectively studied 332 patients between 2002 and 2006; divided in 4 groups reflecting donor and recipient risk.

Results

Non-marginal recipients were less likely to receive a marginal organ (69 of 207, 33%) as compared to marginal recipients, of whom two-thirds received a marginal organ (p < 0.0001). Graft function significantly differed between the groups, but detrimental effect of marginal recipient status on eGFR after 12 months (-6 ml/min/1.73 qm, 95% CI -2 to -9) was clearly smaller than the effect of marginal donor status (-10 ml/min/1.73 qm, 95% CI -7 to -14).

Conclusions

As we were able to show expanded criteria donor has a far bigger effect on long-term graft function than the "extra risk" recipient. Although there have been attempts to define groups of recipients who should be offered ECD kidneys primarily the discussion is still ongoing.     

Neonatal Immune Thrombocytopenia

Background

Neonatal immune thrombocytopenia, a consequence of transplacental transfer of antiplatelet antibodies can result in serious bleeding with disastrous consequences in the otherwise healthy newborn.

Methods

Over 2 years at a service hospital, 5 mothers with chronic autoimmune thrombocytopenia and one with maternal alloimmunisation delivered, which comprised the study sample.

Results

Of these, two ladies suffered episodes of thrombocytopenia in the current pregnancy. They were provided platelet transfusions and intravenous immunoglobulins. All patients delivered vaginally. Cord blood platelet was normal in all cases. Three babies developed thrombocytopenia, two due to autoimmune and one alloimmune pathology. The nadir of thrombocytopenia occurred in 36-72 hours with recovery taking place in 10 days. The clinical manifestations were petechiae, ecchymosis, gastric bleed and oozing from vitamin K injection site. Two of the affected babies were provided intravenous immunoglobulins and one steroids. Only one of the two mothers who suffered thrombocytopenia during pregnancy and was provided intravenous immunoglobulins was associated with neonatal thrombocytopenia, an inconsistent relation. It was also observed that antenatally provided immunoglobulins raised effectively maternal rather than fetal platelet counts. However, postnatal immunoglobulins were efficacious in thrombocytopenic neonates.

Conclusion

Thus inspite of several therapeutic and preventive modalities being described, the optimum management strategy of immune mediated perinatal thrombocytopenia is yet in evolution.Key Words: Immunoglobulins, Immune thrombocytopenia, Neonate     

Mean platelet volume and its relationship with carotid atherosclerosis in subjects with non-alcoholic fatty liver disease

Background

Non-alcoholic fatty liver disease (NAFLD) is linked to an increased risk of cardiovascular disease. Mean platelet volume (MPV), a determinant of platelet activation, is an emerging risk factor for atherothrombosis.

Aims

The aim of this study was to investigate the levels of MPV in subjects with NAFLD having no confounding factors for atherosclerosis such as obesity, diabetes mellitus, and hypertension. In addition, the possible relationship between MPV and carotid artery intima media thickness (CIMT), a well known marker of subclinical atherosclerosis, was also studied.

Methods

MPV and CIMT levels were measured in 60 biopsy-proven NAFLD subjects and 54 healthy controls. Age and sex were similar between two groups.

Results

Body mass index and waist circumference levels were higher in the NAFLD group when compared to the controls. There were no differences between the two groups regarding LDL cholesterol levels, whereas HDL cholesterol levels were lower in the NAFLD group. MPV and CIMT levels were not different between the two groups. According to the correlation analyses, CIMT levels were positively correlated to age in patients with NAFLD. However, no significant correlation was found between MPV and CIMT levels.

Conclusions

The results of this study do not show any difference in MPV levels between subjects with NAFLD and controls. These finding suggests that in the absence of other metabolic risk factors, MPV might not be involved in the mechanism(s) of increased cardiovascular risk in NAFLD.     

Combination of BCL11A siRNA with vincristine increases the apoptosis of SUDHL6 cells

Background

B cell chronic lymphocytic leukemia/lymphoma 11 A (BCL11A) is associated with human B cell malignancy initiation. Our previous study has shown that downregulation of BCL11A mRNA by small interfering RNA (siRNA) is capable of inducing apoptosis in the SUDHL6 cell line. To further explore the effects of BCL11A siRNA on the enhanced cytotoxicity of a chemotherapeutic drug, we investigated the effects of BCL11A siRNA combined with vincristine (VCR) on SUDHL6 cell proliferation and apoptosis.

Methods

Chemically synthesized BCL11A siRNA was transfected into SUDHL6 cells using the HiPerFect Transfection Reagent in combination with VCR. Cell proliferation was measured by the CCK8 assay. The morphology of apoptotic cells was observed with Hoechst 33258 staining. The rate of cell apoptosis was determined by annexin V-fluorescein isothiocyanate/propidium iodide double staining using fluorescence-activated cell sorting (FACS) analysis.

Results

After BCL11A siRNA plus VCR treatment, cell proliferation was significantly decreased in comparison with VCR or BCL11A siRNA treatment alone and negative control siRNA plus VCR treatment (P <0.05). The apoptotic rate of BCL11A siRNA plus VCR treated cells was significantly increased compared with BCL11A siRNA and VCR treatment alone and negative control siRNA plus VCR treatment (P <0.05).

Conclusions

The combination of BCL11A siRNA and VCR increases apoptosis in SUDHL6 cells. Our study implies that BCL11A siRNA in combination with VCR may be a useful approach for improving effective treatment for B cell lymphoma.     

Comparative Study of Blood Cross Matching Using Conventional Tube and Gel Method

Background

Conventionally tube method is used for compatibility and cross matching in transfusion medicine.

Methods

A comparative study was carried out to evaluate the efficacy of conventional tube and gel technique.

Result

Compatibility testing was performed on 1000 blood samples by conventional test tube method and DiaMed gel method. The results were analysed.

Conclusion

The gel method was found to be a rapid and reliable procedure without controls. There was no requirement of wash phase in indirect antiglobulin test and sensitivity and specificity was comparable to spin tube method. We conclude that this technique is a better substitute for spin tube method.Key Words: Compatibility testing, ID gel technique     

Can hormone replacement therapy prior to oocyte donation cycle in women with premature ovarian failure improve pregnancy rate?

Background

Infertility is an important issue in women with Premature Ovarian Failure (POF). With no conclusive treatment available to enhance fertility in these women, it is the use of donor eggs with In-Vitro Fertilization (IVF) which can fulfil their desire to become a mother in a novel way. Hormone replacement therapy (HRT) in POF apart from correcting the endocrine defect also helps in improving the milieu of the uterus by improving its vascularisation and the sub endometrial blood flow. We thus aimed to carry out a study to find out whether hormone replacement therapy if administered prior to the oocyte donation cycle in patients of premature ovarian failure improves the pregnancy rate.

Methods

A comparative study was carried out incorporating 46 subjects with 23 in each group. Group A received HRT prior to their oocyte donation cycle while the second group entered into the oocyte donation programme directly after an artificially induced menstruation.

Results

It was observed that, although the HRT group had a slightly higher pregnancy rate, with a better mean endometrial thickness as compared to the non HRT group it was not statistically significant.

Conclusions

Institution of hormone replacement therapy does improve the vascularisation of the uterus, corrects the histologic features of the uterine lining and makes the endometrium receptive but whether it enhances the pregnancy rate needs to be elucidated with further studies.