A new total hemiface allotransplantation model in rats.

INTRODUCTION: Vascularized composite allotransplantation (VCA), a new reconstructive option for patients suffering from extensive facial defects leads to superior functional and aesthetic outcomes compared to the standard autologous reconstruction. Among VCA recipients, each case involves different facial structures and tissues depending on the patient's injury, thus drawing conclusions on the mechanism of immune interactions between the donor and recipient is challenging. This study introduces a new total hemiface VCA model, including scalp, external ear, mystacial pad, premaxilla, upper/lower lids, nose, and upper/lower lips to evaluate the effect of transplantation of multitissue VCA on the recipient's immune response. MATERIAL AND METHODS: Ten hemiface allotransplantations were performed in two groups between Lewis-Lewis (isograft) and LBN-Lewis (allograft) rats. Cyclosporine A (CsA) monotherapy was applied in the allograft group to prevent rejection. RESULTS: All flaps survived up to 100 days post-transplant. The mean warm ischemia time was 45 minutes. Histological analysis revealed normal bone, cartilage (ear and nose), conjunctiva, palpebra, and eyelashes. Flow cytometry confirmed donor-specific chimerism for T cells (CD4/RT1(n) and CD8/RT1(n)) and B cells (CD45RA/RT1(n)) in the peripheral blood of all rats in the allotransplantation group. At post-transplant day 7, chimerism levels were at 1.68% for CD4/RT1(n) , 0.46% for CD8/RT1(n) and 0.64% for CD45RA/RT1(n). However, chimerism levels for CD4/RT1(n), CD8/RT1(n), and CD45RA/RT1(n) populations decreased at long-term follow-up (at post-transplant day 100) to 0.08%, 0.04%, and 0.23%, respectively. CONCLUSION: The feasibility and long-term survival of the new hemiface VCA transplantation model was confirmed, donor-specific chimerism and post-transplant tissue changes were evaluated.

Mild/minimal stimulation protocol for ovarian stimulation of patients at high risk of developing ovarian hyperstimulation syndrome.

BACKGROUND: Recently, an increased scientific interest was focused on mild approaches for ovarian stimulation in clinical practice. Milder stimulation aims to develop safer and more patient-friendly protocols which are more physiological, less drug use, less expensive and the risks of treatment are highly minimized. AIM: To investigate the efficacy and safety of a mild ovarian stimulation protocol in patients at high risk of developing ovarian hyperstimulation syndrome (OHSS), compared to conventional long down-regulation protocol. SUBJECTS AND METHODS: This a prospective, open, randomized study, included 349 infertile patients considered at high risk of developing OHSS, undergoing in vitro fertilization treatment in two private assisted reproduction centers. The patients were randomized into two groups: group A (n = 148) had a mild/minimal stimulation protocol of recombinant FSH (rFSH) combined with GnRH antagonist. Group B (n = 201) (control group) had a standard long protocol of rFSH combined with GnRH agonist. RESULTS: There was no significant difference observed between the two groups regarding the mean number of oocytes retrieved per patient, mature metaphase II oocytes, fertilization rate, and embryo cleavage rate. Significantly higher implantation rate (21.5 vs 14.5 %) (p < 0.05), pregnancy rate (37.7 vs 23.4 %) (p < 0.05), and delivery rate (32.8 vs 20.1 %) (p < 0.05) were observed in favor of groups A compared to group B. Lower proportion of patients (4.7 %), though not statistically significant, has developed OHSS in group A compared to group B (8.4 %). CONCLUSION: Our study shows that mild stimulation regimen is highly effective for ovarian stimulation of patients who have experienced OHSS complication without increasing the risk of OHSS.

Simultaneous administration of human acidic and recombinant less acidic follicle-stimulating hormone for ovarian stimulation improves oocyte and embryo quality, and clinical outcome in patients with repeated IVF failures.

BACKGROUND: Ovarian stimulation is an integral procedure in assisted reproduction treatment. It is achieved by the administration of exogenous gonadotropins to increase follicular recruitment and oocyte yield. Optimization of ovarian stimulation is an essential prerequisite for the success of IVF treatment. AIM: This study aimed to evaluate the effect of a combined stimulation protocol of human FSH and recombinant FSH, simultaneously administered, on oocyte and embryo quality and clinical outcome. PATIENTS AND METHODS: In a prospective randomized study 197 infertile patients with a history of previous IVF failures for at least 3-5 attempts, were enrolled for an in vitro fertilization treatment. All patients had a standard down-regulation with GnRH analog and were then stimulated with FSH. The patients were matched into three groups: group A (no = 66) received human FSH combined with recombinant FSH in equal doses, simultaneously administered; group B (no = 67) received human FSH alone and group C (no = 64) received recombinant FSH alone. RESULTS: There were significantly higher pregnancy (p < 0.04) and implantation rates (p < 0.03) in favor of group A (hFSH/rFSH) compared to groups B (hFSH) and C (rFSH). A significant increase in the proportion of mature metaphase II oocytes (p < 0.002) and grade 1 embryos (p < 0.03) was observed in group A with respect to group B and C. Significantly higher delivery rate (p < 0.01) was achieved in group A compared to groups B and C. No significant differences were observed between groups regarding miscarriage rate and risk of ovarian hyperstimulation syndrome. CONCLUSIONS: The results show that the combination of human and recombinant FSH for ovarian stimulation may produce a positive effect on follicular development as it improve oocyte quality, embryo development, and ultimately clinical outcome.

First case of transformation for breast fibroadenoma to high-grade malignant phyllodes tumor in an in vitro fertilization patient: misdiagnosis of recurrence, treatment and review of the literature.

INTRODUCTION: Cystosarcoma phyllodes are very rare tumors and may be difficult to diagnose clinically. BACKGROUND: Fibroadenomas have long been considered benign hyperplastic lesions rather than true neoplastic processes. However, previous clonality studies have shown differing results. AIM: to assess diagnostic and treatment options for phyllodes tumor. MATERIALS AND METHODS: A 41-year-old female patient undergoing assisted fertilization treatment. The patient underwent fine needle aspiration biopsy that confirmed fibroadenoma before the IVF attempt. At 17 weeks of gestation, due to an increase in volume of the fibroadenoma, an excisional biopsy was performer that showed a malignant phyllodes tumor. Then she underwent quadrantectomy and chemiotherapy After 1 year there was a recurrence of phyllodes tumors and she underwent mastectomy and chemotherapy. RESULTS: Fibroadenoma that was transformed into high-grade malignant cystosarcoma after ovarian stimulation, relapsed after one year and it was not immediately diagnosed. The patient underwent mastectomy and chemotherapy. DISCUSSION: it is difficult to diagnose recurrence and to determine tele frequency and the right treatment for such a rare cancer, so it is important to report any case in the literature. CONCLUSIONS: We recommend to remove a fibroadenoma before attempting IVF for the risk of malignant transformation.

Misdiagnosed widespread eosinophilic granuloma of the mandible.

Eosinophilic granuloma is the most common expression of Langerhans cell histiocytosis and corresponds with typical bone lesions. Early clinical signs can occur in the mandible and can cause extensive destruction of the periodontal tissues. Pathologic fracture is an unusual finding. A case of misdiagnosed eosinophilic granuloma in a 45-year-old man treated with free fibula flap and implant-supported overdenture prosthesis is reported. Free fibula flap with dental implants is a safe and reliable method for comprehensive functional and aesthetic mandibular defect reconstruction.

Skin-to-skin contact and infant emotional and cognitive development in chronic perinatal distress.

OBJECTIVE: We examined whether the timing of maternal-neonate skin-to-skin contact (SSC) predicts infant emotional and cognitive development in the context of chronic maternal perinatal stress and depressive symptoms. STUDY DESIGN: This secondary analysis included data from a group-based prenatal care clinical trial for 37 pregnant women with low household income. Mothers completed the Perceived Stress Scale (PSS), and the Center for Epidemiologic Studies Depression Scale (CES-D) during the third trimester and postpartum. After birth, they reported timing of SSC, and completed the Infant Behavior Questionnaire-Revised Very Short Form (IBQ-R VSF) (M = 51.7 weeks, SD = 4.2). Increased PSS or CES-D score from the third trimester to post-birth indicates chronic maternal perinatal stress or depressive symptoms compared to a decrease or no change. Using hierarchical regression models, we examined if the timing of SSC makes a unique contribution in predicting infant outcomes in the context of chronic maternal perinatal stress and depressive symptoms. RESULTS: Stress-exposed infants had less negative emotionality if SSC is provided immediately after delivery, less than 10 min after birth. The effect of SSC on effortful control in relation to chronic perinatal stress was not statistically significant. The impact of timing of SSC on negative emotionality or effortful control in relation to chronic perinatal depressive symptoms was not statistically significant. CONCLUSION: This work implies that very early SSC may play a role in later infant emotion regulation process and could act as a protective factor in chronically stressed pregnant women.

Effect of transferring a morphologically impaired embryo with a good quality embryo on the pregnancy and implantation rates.

OBJECTIVE: This study aimed to investigate the effect of transferring embryos with different qualities on pregnancy and implantation rates. PATIENTS AND METHODS: In a retrospective multi-center study we analyzed 761 patients aged ≤ 35 years who had an elective transfer of one or two embryos. Embryos were scored morphologically by their developmental stage into good "A" and impaired "B" embryos. Pregnancy and implantation rates were compared between patients who had a transfer of: one grade "A" embryo; two grade "A" embryos, two embryos one grade "A" plus one grade "B" embryos; one grade "B" embryo and two grade "B" embryos. RESULTS: Higher pregnancy and implantation rates were observed in patients who had received one embryo of grade "A" (34.6%) and two grade "A" embryos (45.2%, 25.85% respectively), compared to patients who received two embryos, one of grade "A" plus one of grade "B" (25%, 13.77% respectively). CONCLUSIONS: Transferring a morphologically and developmentally impaired embryo, significantly lower the implantation chance of the good quality embryo.

Successful pregnancies and deliveries after a simple vitrification protocol for day 3 human embryos.

OBJECTIVE: To evaluate the efficacy and efficiency of freezing cleaved human embryos through vitrification. DESIGN: Clinical study of vitrification of human embryos. SETTING: Assisted reproductive technology centers. PATIENT(S): Thirty-six patients undergoing IVF-ICSI treatment whose surplus embryos were frozen. INTERVENTION(S): Two hundred fifteen surplus embryos vitrified, subsequently thawed, and transferred in natural or controlled cycles. MAIN OUTCOME MEASURE(S): Embryo survival rate after thawing and resultant patient pregnancy rate. RESULT(S): From the 215 vitrified and thawed embryos, 106 survived, with an overall embryo survival rate of 49.3%. The survival rate was higher when embryos were vitrified at the eight-cell stage compared with at the six to seven-cell and six-cell stages (79.2%, 39.7%, and 21.1%, respectively). On average, 2.9 +/- 1.2 embryos per patient were transferred, resulting in 11 pregnancies (30.5%), with an implantation rate of 10.4% per embryo transferred. CONCLUSION(S): Ultrarapid embryo freezing by vitrification of eight-cell stage embryos is a reliable method, as evidenced by high rates of embryo survival and pregnancy, making it a superior alternative to the conventional slow-cooling method.

Birth of a healthy infant after conception with round spermatids isolated from cryopreserved testicular tissue.

OBJECTIVE: To report a case of nonobstructive azoospermia in which round spermatids recovered from thawed testicular tissue were used for injection. DESIGN: Case report. SETTING: Reproductive Medicine Unit, S.I.S.ME.R. PATIENT(S): A 33-year-old azoospermic man. INTERVENTION(S): Intracytoplasmic sperm injection with frozen-thawed spermatids. MAIN OUTCOME MEASURE(S): Fertilization, embryo cleavage, pregnancy, and delivery. RESULT(S): Birth of a healthy, chromosomally normal girl. CONCLUSION(S): Frozen-thawed testicular round spermatids from a patient with a history of incomplete spermatogenesis can maintain their viability and their capacity to fertilize and to lead to full-term pregnancy.

Complications of ethmoidectomy: a survey of fellows of the American Academy of Otolaryngology-Head and Neck Surgery.

A survey regarding complications of sinus surgery was mailed to 6969 otolaryngologists; 3933 responses (56.44%) were obtained, and 3043 of these physicians (77.37%) reported that they performed ethmoidectomy. Completed questionnaires were available for review from 42.21% of all Academy fellows (2942 physicians). Responses were tabulated and summarized question by question. Physicians generally did not rate their residency training in ethmoidectomy highly. The survey confirmed that there has been a marked rise in the frequency of ethmoidectomy and in the amount of training in ethmoidectomy since 1985. Empirical complication rates were calculated for different procedures and time periods. Poisson regression models were then constructed to describe the rate of complications under varying conditions such as the type of surgery performed, time period, experience and training of the surgeon, and type of complication encountered. The models permitted determination of the statistical significance of variables in relation to incidence or complications. The study did not demonstrate a clear and consistent statistical relationship between the incidence of complications, the type of surgery performed, and the quality of training. Moreover, physicians who provided data from record review tended to report higher rates than those who estimated responses. The majority of physicians discussed specific potential complications with their patients before surgery and routinely performed preoperative computed tomography. The study demonstrated that physicians who experienced complications at higher rates were more likely to discuss these complications with patients before surgery.

Zona opening of human embryos using a non-contact UV laser for assisted hatching in patients with poor prognosis of pregnancy.

The aim of this study was to examine the safety and the efficiency of a 'non-contact' UV laser to assist hatching through zona opening of human embryos. Between January and November 1995 we performed zona drilling for assisted hatching using a new laser system (PALM UV Laser microbeam), operating in a 'non-contact' mode to create a hole in the zona pellucida of human embryos. In a randomized study, laser zona opening was applied on embryos from two groups of patients with repeated in-vitro fertilization (IVF) failures (two to four attempts): group A was composed of 107 patients who received mixed embryos (216 laser-treated and 223 not treated) and group B of 72 patients who received 218 laser-treated embryos only. Both groups were compared with a control group of 98 patients whose embryos were not laser treated (n = 407) (group C). The mean ages of all groups (38.1, 38.2 and 37.8 years respectively) and the number of IVF attempts (two to four attempts) were similar. The resulting clinical pregnancies were 39 (36.4%) in group A, 32 (44.4%) in group B and 19 (19.3%) in group C. The implantation rates/embryo were 9.3% in A, 16% in B and 5.1% in the control group. In total, 17 normal babies have been delivered (10 in group A and seven in group B). These results show that laser zona drilling increased the pregnancy and implantation rates in all the treated patients. The increase was slight but significant in patients of group A (P < 0.01 and P < 0.02), it was even higher in the patients of group B (P < 0.05).

Elective cryopreservation of all pronucleate embryos in women at risk of ovarian hyperstimulation syndrome: efficiency and safety.

In a prospective randomized study, we analysed 125 patients at risk of ovarian hyperstimulation syndrome (OHSS), selected in the period between January 1996 and July 1997. All the patients had blood oestradiol concentration >/=1500 pg/ml on the day of human chorionic gonadotrophin (HCG) administration and >/=15 oocytes were collected. The patients were matched in two groups: group A, control group (n = 67), had fresh embryo transfers; group B (n = 58) had cryopreservation of all obtained pronucleate embryos. Pregnancy, live birth rates and the incidence of OHSS were compared between the two groups. There were no significant differences in terms of pregnancies per patient (46.3 versus 48.3%) and live birth rates (38. 8 versus 39.6%). No cases of OHSS occurred in group B, while four patients developed the syndrome in group A. The implantation rate was slightly but not significantly lower in group B (chi2 = 1.03). These results suggest that elective cryopreservation of all zygotes might prevent the risk of OHSS in patients undergoing IVF treatment. In contrast to what has been reported by other authors, our results show that the elective cryopreservation of zygotes does not affect pregnancy and live birth rates.

Zona thinning with the use of laser: a new approach to assisted hatching in humans.

From 1993 to 1994, in our centre, laser-assisted hatching was performed on 2- to 4-cell stage embryos obtained from in-vitro fertilization (IVF) patients. We treated 376 embryos from 96 patients with repeated IVF failures (two to four attempts) (group A) and 397 embryos from 111 patients undergoing IVF for the first time (group B). Embryos were transferred immediately after the laser treatment. Both groups were compared to control groups (A' and B') whose embryos were transferred with intact zona pellucida (ZP). The resulting clinical pregnancies were 41 in A and 44 in B versus 24 in A' and 23 in B' respectively. The pregnancy rates per patient were 42.7 and 39.6% versus 23.1 and 19% in the control groups (P < or = 0.05), while the implantation rates per embryo were 12.2% in A and 11.8% in B versus 7.3% and 7.1%. These results show that laser zona thinning of human embryos at 48 h after egg retrieval significantly increases the implantation and pregnancy rate (P < or = 0.05).

Fertilization with human testicular spermatids: four successful pregnancies.

Between July 1995 and May 1996, 36 patients with non-obstructive azoospermia of secretory origin underwent intracytoplasmic injection of spermatids. A previous histological biopsy was performed on all patients: 15 had spermatogenic arrest, a further 13 had Sertoli cell-only syndrome, and the remaining eight had post-cryptorchidism tubal atrophy. The ejaculate was duly examined and a complete absence of spermatozoa and spermatids was confirmed, with only bacteria and debris being found. Testicular sperm extraction (TESE) was then performed. In 19 out of 36 cases round spermatids only were found, while elongated spermatids were found in the remaining 17. Both round and elongated spermatids were isolated and used for injection. A total of 135 oocytes at metaphase II were recovered from 19 partners and injected with round spermatids, while 123 mature oocytes from 17 partners were injected with elongated spermatids. The number of oocytes fertilized, as judged by the presence of two pronuclei, was 75 (55.5%) and 71 (57.7%) respectively. By 34 h after injection, the number of embryos which had cleaved to the 2-cell stage was 56 (74.6%) with round spermatids and 55 (77.4%) with elongated spermatids. All cleaved embryos were transferred into the uterus of the partners. Clinical pregnancies were established in two cases of round spermatid cycles (10.5%) (both are still ongoing), and three cases of elongated spermatid cycles (17.6%) (two are still ongoing; one was lost after 8 weeks of gestation). Chromosomal analysis showed that all fetuses had a normal karyotype (three male and one female) with no chromosomal abnormalities.

Successful fertilization and pregnancy after injection of frozen-thawed round spermatids into human oocytes.

The effect of cryopreservation on the integrity and fertilizing capacity of round spermatids was studied in two azoospermic patients. In December 1995 the patients, both with maturation arrest of spermatogenesis, were submitted to testicular sperm extraction (TESE) after an extensive examination of their ejaculate. Only round spermatids were found after testicular biopsy. Some of the spermatids were isolated and used for a first injection, while the remainder of the preparation was cryopreserved for successive cycles. Because of the failure of the first attempt, 3 months later, the same two patients were submitted to a second one. The frozen preparation was thawed and examined to evaluate the integrity and the viability of surviving round spermatids. More than 70% of the thawed spermatids were viable for injection. Fifteen oocytes at metaphase II, retrieved from the patients' wives, were microinjected with thawed round spermatids. Eighteen hours after the injection, seven out of 15 oocytes showed normal fertilization, with the presence of two pronuclei. The zygotes were cultured to observe embryonic development. After 48 h, six cleaving embryos had developed to at least the two-cell stage, while one had arrested at the pronuclear stage. At 72 h, the cleaving embryos showed further development to the four- to six-cell stage. They were then transferred into the uterus. After 3 weeks a clinical pregnancy was established in one patient [beta-human chorionic gonadotrophin (beta HCG) concentration was 2100 UI]. At 16 weeks of gestation, chromosomic analysis was performed, which confirmed the presence of a fetus with normal karyotype. The pregnancy is ongoing.

Testicular sperm extraction combined with cryopreservation of testicular tissue in the treatment of azoospermia.

BACKGROUND: The aim of the present study was to verify the feasibility of cryopreserving testicular tissue during the first diagnostic biopsy and then using thawed sperm to inseminate the partner's oocytes. The expected advantages are: (i) minimal risk of not having spermatozoa available at the time of intracytoplasmic sperm injection; (ii) no repeated surgical interventions, and (iii) programming the treatment cycle at the couple's convenience. MATERIALS AND METHODS: Between May 1996 and May 1998, 64 azoospermic patients underwent investigative testicular biopsy combined with cryopreservation of spermatozoa which were retrieved in a simultaneously examined fresh sample. Testicular tissue cryopreservation was carried out in 43 cases (67%) for later intracytoplasmic sperm injection attempts. RESULTS: In all, 23 couples underwent 26 assisted conception cycles; the fertilization rate was 64% with spermatozoa (139/218, 24 cycles), 40% with round spermatids (2/5, 1 cycle), and 69% with elongated spermatids (9/13, 1 cycle). The embryo cleavage rate was 84%. The mean number of embryos replaced in 24 patients was 2.7 +/- 0.7. In 2 cases, embryo quality was very poor, and they were not transferred to the patients. Eight clinical pregnancies resulted (35%/patient and 33%/transferred cycle) with an implantation rate of 14.1%; 2 patients have already delivered and 6 pregnancies are ongoing normally. CONCLUSIONS: Testicular tissue cryopreservation during the first diagnostic biopsy is an alternative to repeated surgical interventions. Patients can initiate an ovarian stimulation cycle, confident of having spermatozoa available. Moreover, since only one straw is routinely used for each intracytoplasmic sperm injection cycle, the frozen tissue remains as a sperm source for multiple attempts.

Diagnostic testicular biopsy and cryopreservation of testicular tissue as an alternative to repeated surgical openings in the treatment of azoospermic men.

Between May 1996 and May 1998, 64 azoospermic patients underwent an investigative testicular biopsy combined with the cryopreservation of spermatozoa which were retrieved from a simultaneously examined fresh sample. Testicular tissue cryopreservation was carried out in 43 cases (67%) for late intracytoplasmic sperm injection (ICSI) attempts. In all, 23 couples underwent 26 assisted conception cycles; the fertilization rate was 64% with spermatozoa (139/218, 24 cycles), 40% with round spermatids (2/5, one cycle), and 69% with elongated spermatids (9/13, one cycle). The embryo cleavage rate was 84%. A mean number of 2.7 +/- 0.7 embryos were replaced in 24 patients. In two cases, embryo quality was very poor and they were not transferred. Eight clinical pregnancies resulted (35% per patient and 33% per transferred cycle) with an implantation rate of 14.1%: two patients have already delivered and six are ongoing. In conclusion, the cryopreservation of testicular tissue during the first diagnostic biopsy is an alternative to repeated surgical openings and permits patients to initiate an ovarian stimulation cycle with the certitude of having spermatozoa available. Moreover, since only one straw is routinely used for each ICSI cycle, the frozen tissue remains as a sperm source for multiple attempts.

Freuencia de la hemoglobinopatía "s" en una muestra de población de la raza negra en Trujillo, Colón / Hemoglobinopathy \"s\" frequency in a population sample of the black race in Trujillo, Colón

Se realizó un estudio descriptivo, transversal y de prevalencia para la deteminación de la frecuencia de la hemoglobinopatía "S" (Hb S) en la población de raza negra que acudió al Hospital Paredes de Trujillo, Colón, de Septiembre de 1990 a Marzo de 1991. Se muestrearon a un total de 829 pacientes de dicha raza distribuidos de la siguiente manera: 266 (32.09//) correspondieron al sexo masculino y 563 (67.91//) al sexo femenino; El mayor porcentaje de pacientes estudiados estaba comprendido entre los 1 y los 29 años de edad con 648 (78.17//) muestras. A todas las muestras se les practicó la prueba de inducción de drepanocitos con metabisulfito de sodio encontrándose un total de 69 (8.32//) muestras positivas a las cuales posteriormente se les realizaron hemolizados con tolueno y luego la prueba de electroforesis de hemoglobina en acetato de celulosa. De las 69 muestras, 54(6.51//) presentaban alteraciones en sus patrones electroforéticos correspondiendo 44 (5.30//) a la hemoglobinopatía SA (HB SA), 9 (1.08//) a la hemoglobinopatía SS (Hb SS) y 1 (0.12//) a la hemoglobinopatía doble heterocigota SC (Hb SC). Los 15 casos restantes presentaron patrones electroforáticos normales