Determinants of transplantation success with cryopreserved ovarian tissue: data from 196 women of the FertiPROTEKT network.

STUDY QUESTION: What are the pregnancy and live birth rates for ovarian tissue transplantation and which factors are associated with the success rate? SUMMARY ANSWER: Pregnancy and live birth rates per transplanted woman are 32.7% and 26.5% and success rate is associated with female age and first versus repeated transplantation. WHAT IS KNOWN ALREADY: Live birth rates after ovarian tissue transplantations have been reported to be between around 24% and 41% per patient. Success rates seem to be negatively associated with increasing female age at the time of tissue cryopreservation and with pelvic radiation. Success rates are apparently not reduced after overnight transportation of ovarian tissue before freezing. STUDY DESIGN, SIZE, DURATION: Registry analysis of 244 transplantations in 196 women, performed by 26 FertiPROTEKT network centres from 2007 to 2019 with follow-up till December 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Orthotopic ovarian tissue transplantations were performed in 196 women, 191 with previous malignant and 5 with previous non-malignant diseases. Size of transplanting centres varied between 1 and 100 transplantations per centre (median: 2). Factors possibly associated with success rate such as female age, first and repeated transplantation, experience of the transplanting centre and overnight transportation of the ovarian tissue before freezing were analysed. MAIN RESULTS AND THE ROLE OF CHANCE: Average age of all 196 transplanted women was 31.3 years (SD 5.2; range 17-44) at the time of cryopreservation of tissue and 35.9 years (SD 4.8; range 23-47) at the time of transplantation. Pregnancy rate was 30.6% (95% CI, 24.2-37.6%) per first transplantation and 32.7% (95% CI, 26.1-39.7%) per patient. Pregnancy rate was higher after first transplantation (30.6% (95% CI, 24.2-37.6%)) compared to second and subsequent transplantations (11.8% (95% CI, 3.3-27.5%)). Live birth rate per first transplantation was 25.0% (95% CI, 19.1-31.7%) and per patient 26.5% (95% CI, 20.5-33.3%). Success rate decreased with increasing age at the time of ovarian tissue freezing. Live birth rate was 28.2% (95% CI, 20.9-36.3%) in women <35 years and 16.7% (95% CI, 7.9-29.3%) in women >35 years. Pregnancy rates after first transplantation were higher in centres who had performed ≥10 transplantations (35.1%) compared to centres with <10 transplantation (25.4%) (P = 0.12). Corresponding live birth rates were 27.0% and 18.6%. Success rates were not different in women with and without overnight transportation of tissue before cryopreservation. LIMITATIONS, REASONS FOR CAUTION: The data were drawn from a registry analysis. Data such as ovarian reserve and premature ovarian insufficiency were not available for all women. Data might be influenced by different follow-up policies of the centres. WIDER IMPLICATIONS OF THE FINDINGS: The study reveals the high potential of ovarian tissue freezing and transplantation, but only if freezing is performed in younger women. The study suggests focus should be placed on the first and not on repeated transplantations. It also opens the discussion of whether transplantation should rather be performed by experienced centres. STUDY FUNDING/COMPETING INTEREST(S): No funding. No competing interests. TRIAL REGISTRATION NUMBER: N/A.

First live birth in China after cryopreserved ovarian tissue transplantation to prevent premature ovarian insufficiency.

OBJECTIVE: This article reports the first live birth after cryopreserved ovarian tissue transplantation to prevent premature ovarian insufficiency in China. METHODS: A patient with myelodysplastic syndrome received ovarian tissue cryopreservation before hematopoietic stem cell transplantation, and six ovarian cortex strips were thawed and transplanted into her peritoneal pocket 2 years later. RESULTS: Pregnancy occurred spontaneously 27 months after grafting, and a healthy girl was born at 38 weeks gestation. Until now, the child has developed normally without any major diseases. CONCLUSIONS: We report the first live birth resulting from ovarian tissue cryopreservation and transplantation in China.

First pregnancy in China after ovarian tissue transplantation to prevent premature ovarian insufficiency.

OBJECTIVE: This article reports the first case of pregnancy after frozen-thawed ovarian tissue transplantation to prevent iatrogenic premature ovarian insufficiency in China. METHODS: Ovarian tissue cryopreservation was performed in a patient with myelodysplastic syndrome (MDS) before multi-agent chemotherapy and hematopoietic stem cell transplantation. Two years later, she showed complete remission from MDS, and six frozen-thawed ovarian tissue strips were transplanted into the peritoneal pocket. RESULTS: The patient's ovarian activity was restored 3 months after transplantation, and pregnancy occurred spontaneously 27 months after grafting. Until now, the pregnancy has progressed for 30 weeks, and the repeated ultrasound showed normal fetal development. CONCLUSION: This is the first pregnancy resulting from ovarian tissue cryopreservation and transplantation in China.

Ovarian tissue cryopreservation and transplantation prevents iatrogenic premature ovarian insufficiency: first 10 cases in China.

OBJECTIVE: The aim of this study was to report on the first 10 cases of ovarian tissue cryopreservation (OTC) and retransplantation (OTCT) in China. METHODS: A retrospective descriptive study was performed of 10 Chinese women with different diseases undergoing OTC/OTCT in the first specialized center in China. Patients' ovarian function and fertility were followed up. RESULTS: The 10 cases included five cases of cervical cancer and one case each of endometrial cancer, breast cancer, rectal cancer, myelodysplastic syndrome, and aplastic anemia, respectively. The average age at OTC was 33.70 years; the time from OTC to OTCT was 15 months. The average number of transplanted ovarian tissue pieces was 4.9, with 9.5 pieces remaining cryopreserved. The OTCT position for nine cases was in a right-sided peritoneal pocket of ovarian fossa, and for one patient was in bilateral pockets. The average time from OTCT to restoration of ovarian function was 3.4 months. One year after OTCT, all ovaries were still functioning normally. In the first case, the function now remains preserved for more than 3 years. So far, the woman who wishes to conceive has no pregnancy. CONCLUSION: Regarding ovarian function, OTC and OTCT were successful and reliable in China's first cryobank. We expect to perform more retransplantations in the near future, which will add to the global data.

Case report of the first successful cryopreserved ovarian tissue retransplantation in China.

Ovarian tissue cryopreservation and retransplantation has been offered as a fertility preservation approach for over a decade. At least 130 live births have been reported after frozen-thawed ovarian tissue transplantation worldwide. The first International Fertility Protection Center in China was established in 2015. Until now no live birth has been reported. However, we are able to report the first Chinese successful retransplantation of cryopreserved ovarian tissue (September 2016) in a woman with squamous cell cervical carcinoma. Restoration of ovarian endocrine function was shown in the third month after transplantation, and after 21 months of follow-up the transplants are still active and maintaining good function. This first report of successful retransplantation represents a milestone in the field of fertility preservation in China.

Practical recommendations for fertility preservation in women by the FertiPROTEKT network. Part II: fertility preservation techniques.

PURPOSE: In addition to guidelines focusing on scientific evidence, practical recommendations on fertility preservation are also needed. METHODS: A selective literature search was performed based on the clinical and scientific experience of the authors. This article (Part II) focuses on fertility preservation techniques. Part I, also published in this journal, provides information on disease prognosis, disease-specific therapy, and risks for loss of fertility. RESULTS: Ovarian stimulation including double stimulation and freezing of oocytes is the best-established therapy providing live birth chances in women < 35 years with high ovarian reserve of around 30-40%. Ovarian tissue freezing is especially useful in young women with good ovarian, if spontaneous conception is favoured and if < 1 week until chemotherapy is provided. Data on success rates are still limited, but this further evolving technique will possibly reach similar success rates as ovarian stimulation. GnRH agonists seem to reduce the risk of premature ovarian failure up to 50%; however, the effect is possibly not long-lasting. Ovarian transposition can easily be combined with freezing of ovarian tissue and is the preferred technique before pelvic radiotherapy. Other techniques, such as in vitro maturation, are limited to women with high ovarian reserve and remain less effective. In addition, procedures such as in vitro growth of follicles, etc. are still experimental. CONCLUSIONS: Fertility preservation in women provides realistic chances of becoming pregnant. The choice of technique needs to be based on the time required, the woman's age, its risks and efficacy, and the individual preference of the patient.

Ninety-five orthotopic transplantations in 74 women of ovarian tissue after cytotoxic treatment in a fertility preservation network: tissue activity, pregnancy and delivery rates.

STUDY QUESTION: What is the success rate in terms of ovarian activity (menstrual cycles) as well as pregnancy and delivery rates 1 year after orthotopic ovarian transplantations conducted in a three-country network? SUMMARY ANSWER: In 49 women with a follow-up >1 year after transplantation, the ovaries were active in 67% of cases and the pregnancy and delivery rates were 33 and 25%, respectively. WHAT IS KNOWN ALREADY: Cryopreservation of ovarian tissue in advance of cytotoxic therapies and later transplantation of the tissue is being performed increasingly often, and the total success rates in terms of pregnancy and delivery have been described in case series. However, published case series have not allowed either a more detailed analysis of patients with premature ovarian insufficiency (POI) or calculation of success rates based on the parameter 'tissue activity'. STUDY DESIGN, SIZE, DURATION: Retrospective analysis of 95 orthotopic transplantations in 74 patients who had been treated for cancer, performed in the FertiPROTEKT network from 2008 to June 2015. Of those 95 transplantations, a first subgroup (Subgroup 1) was defined for further analysis, including 49 women with a follow-up period >1 year after transplantation. Of those 49 women, a second subgroup (Subgroup 5) was further analysed, including 40 women who were transplanted for the first time and who were diagnosed with POI before transplantation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Transplantation was performed in 16 centres and data were transferred to the FertiPROTEKT registry. The transplantations were carried out after oncological treatment had been completed and after a remission period of at least 2 years. Tissue was transplanted orthotopically, either into or onto the residual ovaries or into a pelvic peritoneal pocket. The success rates were defined as tissue activity (menstrual cycles) after 1 year (primary outcome) and as pregnancies and deliveries achieved. MAIN RESULTS AND THE ROLE OF CHANCE: The average age of all transplanted 74 women was 31 ± 5.9 years at the time of cryopreservation and 35 ± 5.2 at the time of transplantation. Twenty-one pregnancies and 17 deliveries were recorded. In Subgroup 1, tissue was cryopreserved at the age of 30 ± 5.6 and transplanted at 34 ± 4.9 years. Ovaries remained active 1 year after transplantation in 67% of cases (n = 33/49), the pregnancy rate was 33% (n = 16/49) and the delivery rate was 25% (n = 12/49). In Subgroup 5, tissue was cryopreserved at the age 30 ± 5.9 years and transplanted at 34 ± 5.2 years. Ovaries remained active 1 year after transplantation in 63% of cases (n = 25/40), the pregnancy rate was 28% (n = 11/40) and the delivery rate was 23% (n = 9/40). The success rates were age dependant with higher success in women who cryopreserved at a younger age. In Subgroup 5, tissue was exclusively transplanted into the ovary in 10% (n = 4/40) of women and into a peritoneal pocket in 75% (n = 30/40), resulting in spontaneous conceptions in 91% of patients (n = 10/11). LIMITATIONS, REASONS FOR CAUTION: The data were drawn from a retrospective analysis. The cryopreservation and transplantation techniques used have changed during the study period. The tissue was stored in many tissue banks and many surgeons were involved, leading to heterogeneity of the procedures. However, this does reflect the realistic situation in many countries. Although patients with POI were evaluated before transplantation to allow specific analysis of the transplanted tissue itself, the possibility cannot be excluded that residual ovarian tissue was also reactivated. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest case series worldwide to date and it confirms that cryopreservation and transplantation of ovarian tissue can be a successful option for preserving fertility. Persistent tissue activity 12 months after transplantation suggests that the pregnancy and delivery rates may increase further in the future. As transplantation into the peritoneum results in a high success rate, this approach may be an alternative to transplantation into the ovary. However, in order to establish the best transplantation site, a randomized study is required. STUDY FUNDING/COMPETING INTEREST: This study was in part funded from the Deutsche Forschungsgemeinschaft (# DI 1525) and the Wilhelm Sander Foundation (2012.127.1) and did not receive any funding from a commercial company. No competing interests. TRIAL REGISTRATION NUMBER: None.

Gynaecological endoscopic evaluation of 4% icodextrin solution: a European, multicentre, double-blind, randomized study of the efficacy and safety in the reduction of de novo adhesions after laparoscopic gynaecological surgery.

BACKGROUND: Gynaecological laparoscopic surgery outcomes can be compromised by the formation of de novo adhesions. This randomized, double-blind study was designed to assess the efficacy and safety of 4% icodextrin solution (Adept(®)) in the reduction of de novo adhesion incidence compared to lactated Ringer's solution (LRS). METHODS: Patients undergoing laparoscopic surgery for removal of myomas or endometriotic cysts were treated with randomized solution as an intra-operative irrigant and 1l post-operative instillate. De novo adhesion incidence (number of sites with adhesions), severity and extent were independently scored at a second-look procedure and the efficacy of the two solutions compared. The effect of surgical covariates on adhesion formation was also investigated. Initial exploratory analysis of individual anatomical sites of clinical importance was progressed. RESULTS Of 498 patients randomized, 330 were evaluable (160 LRS--75% myomectomy/25% endometriotic cysts; 170 Adept--79% myomectomy/21% endometriotic cysts). At study completion, 76.2% LRS and 77.6% Adept had ≥ 1 de novo adhesion. The mean (SD) number of de novo adhesions was 2.58 (2.11) for Adept and 2.58 (2.38) for LRS. The treatment effect difference was not significant (P = 0.909). Assessment of surgical covariates identified significant influences on the mean number of de novo adhesions regardless of treatment, including surgery duration (P = 0.048), blood loss in myomectomy patients (P = 0.019), length of uterine incision in myomectomy patients (P < 0.001) and number of suture knots (P < 0.001). There were 15 adverse events considered treatment-related in the LRS patients (7.2%) and 18 in the Adept group (8.3%). Of 17 reported serious adverse events (9 LRS; 8 Adept) none were considered treatment-related. CONCLUSIONS: The study confirmed the safety of Adept in laparoscopic surgery. The proportion of patients with de novo adhesion formation was considerably higher than previous literature suggested. Overall there was no evidence of a clinical effect but various surgical covariates including surgery duration, blood loss, number and size of incisions, suturing and number of knots were found to influence de novo adhesion formation. The study provides direction for future research into adhesion reduction strategies in site specific surgery.

[Perioperative patient management. Evaluation of subjective stress and demands of patients undergoing elective gynaecological surgery]. / Perioperatives Patientenmanagement. Evaluation von subjektiver Beanspruchung bei Patientinnen mit elektiven gynäkologischen Operationen.

BACKGROUND: The aim of this investigation was to assess the extent of stress and demands in patients during preparation for general anesthesia for elective surgical procedures. PATIENTS AND METHODS: A total of 52 female patients scheduled for elective gynecological surgery under general anesthesia were included in this prospective study. The extent and time course of actual demands describing perceived emotional stress was assessed at close intervals using the German version of the Questionnaire for Actual Demands (KAB). Pre-operative and postoperative anxiety was assessed using part one of Spielberger's state-trait-anxiety inventory (STAI-X1). This was compared to hemodynamic (heart rate und blood pressure) and endocrinal stress parameters [cortisol concentration in serum and saliva, prolactin and dehydroepiandrosteronesulfate (DHEA-S) in serum]. Postoperatively, all patients were asked to rate the quality of care during preparation for general anesthesia. RESULTS: The extent of patients' demands and stress during preparation for general anesthesia could be quantified by the short questionnaire for the actual demands (KAB). So-called objective stress parameters like hemodynamic and endocrinal data alone did not correlate with perceived stress. However, the subjective information correlated with the nature of the underlying diagnosis. The postoperative assessment of quality of care during preparation for general anesthesia did not correlate with the course of actual demands and stress. CONCLUSION: In future studies assessing the perioperative management of patients and quality of care, standardized testing questionnaires should be preferred, instead of vegetative parameters alone, to reliably evaluate perioperative demands and stress in surgical patients.

Pesticide exposure and self-reported Parkinson's disease in the agricultural health study.

Previous studies based on limited exposure assessment have suggested that Parkinson's disease (PD) is associated with pesticide exposure. The authors used data obtained from licensed private pesticide applicators and spouses participating in the Agricultural Health Study to evaluate the relation of self-reported PD to pesticide exposure. Cohort members, who were enrolled in 1993-1997, provided detailed information on lifetime pesticide use. At follow-up in 1999-2003, 68% of the cohort was interviewed. Cases were defined as participants who reported physician-diagnosed PD at enrollment (prevalent cases, n = 83) or follow-up (incident cases, n = 78). Cases were compared with cohort members who did not report PD (n = 79,557 at enrollment and n = 55,931 at follow-up). Incident PD was associated with cumulative days of pesticide use at enrollment (for highest quartile vs. lowest, odds ratio (OR) = 2.3, 95% confidence interval: 1.2, 4.5; p-trend = 0.009), with personally applying pesticides more than half the time (OR = 1.9, 95% confidence interval: 0.7, 4.7), and with some specific pesticides (ORs > or = 1.4). Prevalent PD was not associated with overall pesticide use. This study suggests that exposure to certain pesticides may increase PD risk. Findings for specific chemicals may provide fruitful leads for further investigation.

Clinical evaluation of a viscoelastic gel for reduction of adhesions following gynaecological surgery by laparoscopy in Europe.

BACKGROUND: Commonly used adhesion prevention devices either cannot be applied or are difficult to use via laparoscopy. A viscoelastic gel was developed specifically for adhesion prophylaxis during minimally invasive surgery. METHODS: Randomized, third party-blinded, parallel-group design conducted at four centres. Patients (18-46 years old) underwent laparoscopic surgery with second look 6-10 weeks later. Viscoelastic gel coated adnexa and adjacent tissues. Blinded reviews of videotapes were quantified by American Fertility Society (AFS) adhesion scores. RESULTS: In 25 treatment patients, surgery was performed on 45 adnexa. Coverage of surgical sites at risk for adhesions was typically accomplished with approximately 15 ml of viscoelastic gel which was delivered in approximately 90 s. In 24 control patients, surgery alone was performed on 41 adnexa. Treated adnexa showed a decrease in AFS score (11.9-9.1). In contrast, control adnexa showed an increase in AFS score (8.8-15.8). This difference in second-look AFS scores (42% reduction) is significant (P<0.01). Ninety-three per cent of treated adnexa did not have a worse adhesion score in contrast to 56% of control adnexa. Combining scores into prognostic categories also show significant treatment effect of the viscoelastic gel (P<0.01). CONCLUSION: Viscoelastic gel was easy to use via laparoscopy and produced significant reduction in adnexal adhesions. It provides benefits to patients undergoing gynaecological surgery.

Detection and mapping of intraabdominal adhesions by using functional cine MR imaging: preliminary results.

PURPOSE: To identify and map intraabdominal adhesions by using functional cine magnetic resonance (MR) Imaging. MATERIALS AND METHODS: Twenty-seven patients suspected of having intraabdominal adhesions were examined. Section-by-section dynamic depiction of induced visceral slide throughout the whole abdomen was achieved by using a transverse or sagittal true fast imaging with steady-state precession sequence. Location and type of diagnosed adhesions were documented by using the nine segments of the abdominal map. These criteria and intraoperative results were compared in 13 patients. RESULTS: MR images depicted a total of 42 intraabdominal adhesions; 21 (50%) were in the lower abdomen. The most common types of adhesions were located between the ventral abdominal wall and small-bowel loops (n = 10 [24%]) and between adjacent small-bowel loops (n = 9 [21%]). Comparison with the intraoperative results showed a sensitivity of 87.5% and a specificity of 92.5%. MR imaging was most accurate in depicting adhesions to the abdominal wall (15 [94%] of 16) and subperitoneal space (eight [100%] of eight). The presence of adhesions between bowel loops was overestimated. CONCLUSION: Detection of visceral slide at functional cine MR imaging is easy to perform and represents a well-tolerated and accurate procedure for use in the identification of intraabdominal adhesions in patients with chronic pain and equivocal clinical findings.

Assessment of 5-aminolevulinic acid-induced porphyrin fluorescence in patients with peritoneal endometriosis.

OBJECTIVE: The purpose of this study was to examine the diagnostic potential for patients with endometriosis of porphyrin fluorescence after oral administration of 5-aminolevulinic acid. STUDY DESIGN: Fifteen women referred for laparoscopy because of suspected endometriosis received 1 or 10 mg/kg 5-aminolevulinic acid orally. After 1.5 to 6 hours endoscopic fluorescence spectral analysis and video inspection were performed. RESULTS: With 10 mg/kg 5-aminolevulinic acid and application intervals of >3 hours we observed a significantly higher porphyrin fluorescence in active peritoneal endometriosis than in adjacent normal peritoneum. Pigmented and nodular endometriosis showed weak to negative fluorescence. A strong fluorescence of the fimbrial mucosa was seen. A 1-mg/kg dose of 5-aminolevulinic acid was insufficient for fluorescence diagnosis. No side effects were recorded. CONCLUSION: Porphyrin fluorescence after oral administration of 5-aminolevulinic acid may be beneficial in diagnosis of peritoneal endometriosis. The strong fluorescence of fimbrial mucosa may limit the applicability of this technique in young women, however, because phototoxic damage cannot be excluded at present.

[A new vacuum extraction system with a ball joint and detachment warning--in vitro studies and clinical use]. / Untersuchungen an einem neuen Saugglockensystem mit Kugelgelenk und Abrisswarnung--In-vitro-Studien und klinische Anwendung.

BACKGROUND: The vacuum extractor is used in about 5% of deliveries. It is associated with a lower maternal morbidity than is forceps extraction. On the other hand, cephalhematomas, hyperbilirubinemia and cerebral hemorrhages in the baby are observed more frequently. The sudden detachment of the vacuum extractor with appreciable fluctuations in intracranial pressure in the baby is especially dangerous. In order to improve the conventional Malmström system, we have developed a new vacuum extractor and investigated its handling in vitro and in clinical application. PATIENTS AND METHODS: The essential constructional principle of the new vacuum extractor consists in a pivot lowered by ball bearings and a volume reduction of one third. Moreover, in two-chamber vacuum it is possible to give a warning of sudden detachment. The possible tractional force in kiloponds was determined at various angles (0 degree, 15 degrees, 30 degrees und 45 degrees) comparing the Malmström extractor with the new one and two-chamber system in a standardized apparatus. In addition, the new vacuum extractor was also used clinically in 43 women; besides the obstetric parameters, the handling was also appraised. RESULTS: In the in-vitro experiments, a distinct decrease of the possible tractional force with increasing angles was shown for the Malmström extractor (0 degree--15.7 kp, 15 degrees--12.7 kp, 30 degrees--8.6 kp, 45 degrees--7.3 kp). The values for the new one-chamber system were significantly greater from a tractional angle of 15 degrees (0 degree--15.6 kp, 15 degrees--14.4 kp, 30 degrees--14.0 kp, 45 degrees--13.8). The clinical application of the new vacuum system was unproblematic and confirmed the feasibility of good traction. A very much smaller caput succedaneum was found in the baby. Especially in the training situation, the warning system enables a good surveillance before sudden detachment, but reduces the possible tractional force. CONCLUSIONS: The new vacuum system appears to enable the vaginal surgical delivery to be improved compared to the conventional Malmström extractor. After these promising approaches, a multicenter study was commenced in order to enable better evaluation of their clinical significance.

[Effects of tubal sterilization]. / Auswirkungen der operativen Kontrazeption.

OBJECTIVE: Besides manifestations of hormonal deficits, psychological problems are also known as possible negative effects of tubal sterilization (here termed "operative contraception"--OC). It is generally assumed that the age at time of operation and the number of children play a crucial role in enabling the patient to come to terms with surgical contraception. We investigated whether these patients were satisfied and the frequency of a desire for refertilization as well as further factors possibly affecting our patients. PATIENTS AND METHODS: A standardized questionnaire was sent to 274 women in whom surgical contraception was performed from 1984 to 1990 in our hospital. Besides physical symptoms, the questions mainly inquired as to satisfaction, degree of regret and desire for refertilization. RESULTS: 5.4% of women were not satisfied with the operation. 13.7% of the patients regretted the operative contraception and 6.5% wished to have refertilization. The negative appraisal did not correlate with the number of children and age at the time of operative contraception. Altogether, satisfaction was very much greater in patients who had completed family planning than in patients who had received operative contraception for medical reasons. Appraisal of operative contraception was especially negative in women in whom the operation had been performed on the occasion of a cesarean section. CONCLUSION: Our follow-up investigation confirmed that operative contraception was experienced as being very liberating by most women and was accordingly appraised positively on the whole. The number of children and age only played a subordinate role in how patients came to terms with their situation. For a positive experience of operative contraception, the time of the operation appears to be of major importance. In particular, "favorable opportunities" on the occasion of cesarean section and the if anything doubtful need for this measure in the condition after prior cesarean sections must be avoided, since in these cases a free decision in favor of operative contraception, which the woman concerned feels to be autonomous, is not possible.

Photodynamic therapy of vulvar intraepithelial neoplasia using 5-aminolevulinic acid.

Photodynamic (PDT) therapy is a relatively new technique with unique properties that make it attractive for the local treatment of superficial epithelial disorders. The objective of this study was to investigate the clinical response of PDT with the photosensitizing agent 5-aminolevulinic acid (5-ALA) in patients with vulvar intraepithelial neoplasia (VIN) grades 1 to 3. Twenty-five patients with 111 lesions of VIN 1-3 were topically sensitized with 10 ml of a 20% solution of 5-ALA and treated with 57 cycles of laser light at 635 nm (100 J/cm(2)). Seventy (64%) of the 111 VIN lesions regressed after various PDT cycles. A complete response was achieved in 13 patients (52%) with 27 lesions. All patients with VIN 1 and mono- and bifocal VIN 2-3 showed complete clearance. However, a complete response could be achieved in only 4 (27%) of 15 women with multifocal VIN 2-3, whereas a partial response was noted in 9 of these patients with a total of 70 lesions, out of which 44 (63%) lesions disappeared. No response was seen in 2 patients with multifocal VIN 3. Histological assessment of the fluorescence-directed biopsies revealed that increased pigmentation and hyperkeratosis of the lesions were associated with low response rates. PDT using 5-ALA represents an alternative treatment modality for VIN which is easy to perform and has the advantage of minimal tissue destruction, low side effects and excellent cosmetic results. However, multifocal VIN disease with pigmented and hyperkeratinic lesions remains difficult to treat.

[Congenital skull depression. Case report and review of the literature]. / Konnatale Schädelimpression. Fallbericht und Literaturübersicht.

A 40-week gestational age infant was delivered by cesarean section because of intense contractions and pathological fetal heart rate pattern. The umbilical artery pH was 7.03, Apgar scores were 1/4/7 at 1, 5 and 10 min of age. The 3,250-gram infant had a skull depression of 5 x 7 cm in the left temporal-parietal region with a depth of 1.5 cm. There were no edemas or hematomas in this area; neurological examination was normal. A CT scan did not show a fracture, but the cortex below the depression appeared slightly compressed. At the age of 11 days, the depressed part of the parietal squama was surgically elevated. The child was discharged in good condition 8 days later and remained well at a 6-month follow-up examination.

Photodynamic therapy in women with cervical intraepithelial neoplasia using topically applied 5-aminolevulinic acid.

Photodynamic therapy (PDT) is a novel treatment modality that produces local tissue necrosis with laser light after prior administration of a photosensitizing agent. We performed a study of topically applied 5-aminolevulinic acid (5-ALA) in the photodynamic treatment of women with high-grade cervical intraepithelial neoplasia (CIN) using fixed 5-ALA doses and application protocols derived from previous in vitro and in vivo results. Three to 5 hr prior to PDT, 10 ml of a 20% solution of 5-ALA was topically applied using a cervical cap. PDT was performed with irradiation of 100 J/cm2 at an irradiance of 100-150 mW/cm2 with an argon-ion-pumped dye laser at 635 nm. For the endocervix, a specifically designed cylindrical applicator was used. Ten treatment cycles of PDT using 5-ALA were performed in 7 patients with high-grade CIN. Non-thermal laser treatment with 100-150 mW/cm2 was well tolerated. Local toxicity was minor as several patients reported burning sensations and vaginal discharge, but no necrosis, sloughing or scarring occurred. After 3 months, a significant reduction in the size of the ectocervical CIN lesions was noted in only 3 patients, who underwent a second PDT cycle. However, no significant improvement in CIN lesions was noted since cold knife conization revealed persistent CIN in all 7 cases. Therefore, PDT after topical application of 5-ALA using an irradiation of 100 J/cm2 produces only minimal side effects. However, it does not appear to be effective in treating CIN.

Photodynamic therapy of vulvar lichen sclerosus with 5-aminolevulinic acid.

OBJECTIVE: To evaluate the therapeutic effect of photodynamic therapy on vulvar lichen sclerosus. METHODS: Twelve women with lichen sclerosus were enrolled in a prospective, single-arm pilot study. Four to 5 hours before photodynamic therapy, 10 mL of a 20% solution of 5-aminolevulinic acid was applied topically to the vulva. Photodynamic therapy was administered with an irradiation of 80 J/cm2 at an irradiance of 40-70 mW/cm2. Light with a wavelength of 635 nm was delivered by an argon ion-pumped dye laser. The degree of pruritus was evaluated using a horizontal visual analog scale before and after 6-8 weeks, and patients were followed tri-monthly after photodynamic therapy. RESULTS: Two women underwent two cycles of photodynamic therapy, one underwent three cycles, and the remaining nine women underwent one cycle each. Treatment was tolerated moderately well, with eight patients not requiring any analgesia; three treated with opioids intravenously during the procedure, due to burning sensations; and one undergoing separation of adhesions under general anesthesia. Minimal local toxicity included vulvar erythema but no necrosis, sloughing, or scarring. No generalized cutaneous photosensitivity was present. Six to 8 weeks after photodynamic therapy, pruritus significantly improved in ten of the 12 women. A prolonged effect of photodynamic therapy was reported, with a mean of 6.1 months. CONCLUSION: Photodynamic therapy after topical application of 5-aminolevulinic acid produced statistically significant relief of symptoms of vulvar lichen sclerosus for an average of 6.1 months with minimal side effects.