Accuracy of sonography for non-invasive detection of ovarian and deep endometriosis using #Enzian classification: prospective multicenter diagnostic accuracy study.

OBJECTIVE: To compare the preoperative detection of endometriosis using transvaginal sonography (TVS) supplemented by transabdominal sonography (TAS) with surgical assessment of disease, using the #Enzian classification for endometriosis. METHODS: This was a prospective multicenter diagnostic accuracy study of women undergoing TVS/TAS and radical surgery for deep endometriosis (DE) at different tertiary referral centers. The localization and grade of severity of the endometriotic lesions and adhesions were described according to the criteria of the #Enzian classification, both at preoperative ultrasound examination and during surgery. According to the #Enzian classification, the small pelvis is divided into three compartments for DE: A (rectovaginal septum and vagina); B (uterosacral and cardinal ligaments, parametrium and pelvic sidewalls); and C (rectum). In addition, further locations (F) are classified as adenomyosis (FA), urinary bladder involvement (FB) and ureteric involvement with signs of obstruction (FU). Other intestinal locations (FI) and other extragenital locations (FO) are also included. Ovarian endometriosis and adhesions at the level of the tubo-ovarian unit are listed as O and T, respectively. The #Enzian grade of severity (Grade 1-3) was determined for #Enzian compartments O, T, A, B and C based on the size of the lesion or the severity of the adhesions. Concordance between preoperative assessment using TVS/TAS and evaluation at surgery was assessed. The sensitivity, specificity, positive and negative predictive values and accuracy of TVS/TAS in the detection of endometriotic lesions/adhesions in the different #Enzian compartments were calculated. RESULTS: In total, 745 women were included in the analysis. Preoperative TVS/TAS and surgical findings showed a concordance rate ranging between 86% and 99% for the presence or absence of endometriotic lesions/adhesions, depending on the evaluated #Enzian compartment. The concordance rate between TVS and surgery ranged between 71% and 92% for different severity grades, in #Enzian compartments O, T, A, B and C. Determining the presence or absence of adhesions at the level of the tubo-ovarian unit and classifying them accurately as Grade 1, 2 or 3 on TVS was more difficult than determining the presence and severity of endometriotic lesions in #Enzian compartments O, A, B and C. The sensitivity of TVS/TAS for the detection of endometriotic lesions ranged from 50% (#Enzian compartment FI) to 95% (#Enzian compartment A), specificity from 86% (#Enzian compartment Tleft ) to 99% (#Enzian compartment FI) and 100% (#Enzian compartments FB, FU and FO), positive predictive value from 90% (#Enzian compartment Tright ) to 100% (#Enzian compartment FO), negative predictive value from 74% (#Enzian compartment Bleft ) to 99% (#Enzian compartments FB and FU) and accuracy from 88% (#Enzian compartment Bright ) to 99% (#Enzian compartment FB). CONCLUSIONS: The localization and severity of endometriotic lesions/adhesions, as described and classified according to the #Enzian classification, can be diagnosed accurately and non-invasively using TVS/TAS. The #Enzian classification provides a uniform classification system for describing endometriotic lesions, which can be used both at TVS/TAS and during surgical evaluation. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

MRI technique for the preoperative evaluation of deep infiltrating endometriosis: current status and protocol recommendation.

Endometriosis is a common cause of chronic pelvic pain and infertility. It is defined as the occurrence of endometrial tissue outside the uterine cavity and can manifest as a peritoneal, ovarian or infiltrating form, the latter being referred to as deep infiltrating endometriosis (DIE). Surgery is essential in the treatment of DIE and depending on the severity of the disease, surgery can be difficult and extensive. Beside clinical examination and ultrasound, magnetic resonance imaging (MRI) has proven its value to provide useful information for planning surgery in patients with suspected DIE. To optimise the quality of MRI examinations, radiologists have to be familiar with the capabilities and also the limitations of this technique with respect to the assessment of DIE. MRI yields morphological information by using mainly T1- and T2-weighted sequences, but can also provide functional information by means of intravenous gadolinium, diffusion-weighted imaging or cine-MRI. In this article, these techniques and also adequate measures of patient preparation, which are indispensable for successful MRI imaging for the preoperative evaluation of DIE, are reviewed and a comprehensive protocol recommendation is provided.

Endometrioid adenocarcinoma arising from adenomyosis: a case report.

BACKGROUND: Endometriosis is most commonly found in the peritoneum of the lesser pelvis and in the genital tract (in the ovaries). Its malignant transformation is quite rare, which usually appears in patients who previously underwent surgical procedures aimed at treating endometriosis. Years of hormone substitution (unopposed estrogen therapy) is also considered to have a role. According to the present authors' current knowledge, these are mostly well-differentiated tumors with low malignancy, which are primarily treated surgically. CASE: In the present case the authors present a 73-year-old female patient who underwent a laparotomy due to abdominal pain and a mass in the lesser pelvis. The authors performed hysterectomy along with bilateral adnexectomy and omental resection. The histological examination of the specimens verified an endometrial adenocarcinoma formed on the ground of adenomyosis and the endometrial adenocarcinoma of the left ovary. CONCLUSION: The malignant transformation of endometriosis is rare, and the mechanisms how it develops on the grounds of adenomyosis is currently unclear.

Percutaneous minimal-access fetoscopic surgery for spina bifida aperta. Part II: maternal management and outcome.

OBJECTIVE: To assess maternal morbidity and outcome in women undergoing minimal-access fetoscopic surgery for spina bifida aperta. METHODS: This was a retrospective study of 51 women undergoing minimal-access fetoscopic surgery to improve postnatal neurological outcome of spina bifida aperta, at a mean gestational age of 24 weeks, at our center between July 2010 and June 2013. We analyzed various perioperative complications of surgery, namely: maternal and fetal death, need for maternal blood transfusion, placental abruption, pulmonary edema, spontaneous labor, oligohydramnios, chorioamnionitis, chorioamniotic membrane separation, duration of hospitalization, amniotic fluid leakage, gestational age at delivery and status of hysterotomy site. RESULTS: In none of the 51 women was there maternal demise, spontaneous labor, placental abruption or a need for maternal blood transfusion in the perioperative period. Chorioamniotic membrane separation occurred in one patient, mild pulmonary edema occurred in one and oligohydramnios occurred in seven. All fetuses survived surgery, but there was one very early preterm delivery 1 week after the procedure and this neonate died immediately, from early postoperative chorioamnionitis. Amniotic fluid leakage occurred in 43 patients, at a mean gestational age of 29.7 (range, 22.6-37.3) weeks; two of these patients developed chorioamnionitis. Duration of maternal hospitalization after surgery was 7.2 (range, 4-12) days. Mean gestational age at delivery was 33 (range, 24.6-38.1) weeks. All abdominal and uterine trocar insertion sites healed well. CONCLUSION: Minimal-access fetoscopic surgery for spina bifida aperta is apparently safe for most maternal patients. Despite the common occurrence of amniotic leakage, the majority of women deliver beyond 32 weeks of gestation.

Complementary and alternative medicine (CAM) in obstetrics and gynaecology: a survey of office-based obstetricians and gynaecologists regarding attitudes towards CAM, its provision and cooperation with other CAM providers in the state of Hesse, Germany.

PURPOSE: Whereas we have some information on complementary medicine in the field of oncology, little is known about complementary medicine in the field of obstetrics and gynaecology especially outside of hospitals. METHODS: All office-based obstetricians and gynaecologists in the state of Hesse, Germany, were contacted and asked to fill in an assessment form regarding cooperation in the field of complementary and alternative medicine (CAM), as well as the perceived efficacy of various CAM methods for a number of pathological conditions in the field of obstetrics and gynaecology. RESULTS: It was found that more than half of Hessian office-based obstetricians and gynaecologists had existing cooperation regarding CAM, especially with colleagues, but also midwives, pharmacists, physiotherapists, and health practitioners. The probability of cooperation was significantly inversely associated with age. It was found that the probability for advising CAM differed between various health problems. The following CAM methods were considered reasonable for the treatment of different conditions: phytotherapy for climacteric complaints and premenstrual syndrome; homoeopathy for puerperal problems; acupuncture and traditional Chinese medicine for complaints during pregnancy; and dietary supplements for the side effects of cancer therapy. CONCLUSIONS: The analysis shows that there is much cooperation in the field of CAM. Comparison between physicians' perceived efficacy of CAM methods and objective findings shows that there is a need for the provision of valid information in the field.

Implementation of certified endometriosis centers: 5-year experience in German-speaking Europe.

The idea of quality improvement in the management of endometriosis has been brought to attention throughout Europe. This - first and foremost - includes the implementation of centers specialized in treating endometriosis. This leads to qualification of both physicians and other medical staff, enforcement of research efforts, and informing the patients, the public, politicians, healthcare providers, and industry. Given limited budgets, focusing on the existing national commitment may be the first step.

A new variable-view rigid endoscope evaluated in advanced gynecologic laparoscopy: a pilot study.

BACKGROUND: This pilot study aimed to evaluate the optical performance and clinical handling of a new variable-view rigid endoscope with angulation from 0 º to 120 º in gynecologic laparoscopic surgery. METHODS: The EndoCAMeleon endoscope was assessed by experienced surgeons and assistants during a variety of advanced gynecologic laparoscopic procedures. After each procedure, both the surgeon and the assistant each completed questionnaires designed to assess the endoscope's ease of handling and optical performance. RESULTS: The endoscope was assessed during 21 advanced procedures. Questionnaire responses confirmed surgeon and assistant satisfaction with the mechanical handling and vision provided by the endoscope. In particular, the ability to vary the viewing angles enabled the surgeon to visualize the surgical site without moving the endoscope shaft. CONCLUSIONS: The new endoscope performed well in the hands of experienced surgeons and assistants undertaking advanced procedures. The variable-view rigid endoscope allows the use of visual ports during primary port entry and enhances vision. Further study is required to evaluate its performance in routine practice.

Transvaginal NOTES with semi-rigid and rigid endoscopes that allow adjustable viewing angles.

PURPOSE: To evaluate semi-rigid and rigid endoscopes for transvaginal NOTES surgery. METHODS: One rigid endoscope (EndoCAMeleon, KARL STORZ GmbH & Co. KG, Tuttlingen Germany) and one semi-rigid endoscope (EndoEYE LTF-VH, Olympus Deutschland GmbH, Hamburg, Germany) that allow adjustable viewing angles have been used during four transvaginal gynecological NOTES procedures for chronic pelvic pain and infertility. RESULTS: Feasibility of transvaginal access to enter the abdominal cavity was shown. Posterior peritoneum, ovaries and tubal patency were evaluated. The evaluated endoscopes did not overcome the inability to explore the anterior pelvic structures. CONCLUSIONS: Rigid and semi-rigid endoscopes that allow adjustable viewing angles during transvaginal NOTES approaches cannot explore the whole pelvic anatomical structures.

Establishing transvaginal NOTES for gynecological and surgical indications: benefits, limits, and patient experience.

Gynecologists have been performing transvaginal surgery for over a century and consequently the transvaginal approach was advocated for establishing natural orifice transluminal endoscopic surgery (NOTES) in gynecological and surgical practice. From 2008 the NOTES alternative has been offered to selected patients. Transvaginal cholecystectomies were intended in 13 patients and completed in 12. Various additional procedures were performed. All surgical procedures and postoperative courses were uneventful. The mean operating time for transvaginal cholecystectomy only was 88.4 minutes (standard deviation [SD] 17.3). A questionnaire was posted to the patients after a mean follow-up of 8.5 months. Patients primarily chose transvaginal NOTES because of the lack of scarring. Vaginal sensation was not affected. Patients perceived transgastric, transvesical, and transrectal surgery to be less acceptable approaches. The feasibility of transvaginal NOTES was proven for different indications. Patients' experiences and perceptions concerning transvaginal NOTES were excellent.

Uterine surgery in postpartum hemorrhage.

Uterine atony accounts for the majority of primary postpartum hemorrhage. Timely recognition and intervention are fundamental in preventing serious maternal morbidity and mortality. Combinations of conservative manual and medical therapies are adequate and successful treatment options in most cases. However, when the hemorrhagic process continues and when either clotting abnormalities or hemodynamic instability develop, the next step must be an invasive intervention. Depending on the mode of delivery a vaginal approach (i.e. curettage and uterine packing) after spontaneous delivery or an abdominal surgical approach (i.e. compression sutures and systematic devascularization) after a Cesarean delivery can be performed. Uterine compression sutures are especially highly effective and a straightforward and easy emergency procedure which conserves fertility. The ultima ratio in all cases of persistent haemorrhage after conservative and uterus preserving surgical therapy is the emergent hysterectomy. It might be of advantage to perform a subtotal or supracervical hysterectomy compared to a total hysterectomy in an emergency setting.

A safety and efficacy study of a resorbable hydrogel for reduction of post-operative adhesions following myomectomy.

BACKGROUND: This multicenter, randomized, single-blind study assessed the safety and efficacy of a resorbable hydrogel ('Hydrogel') for the reduction of post-operative adhesion formation following myomectomy. METHODS: Women (n = 71) who were undergoing laparoscopic (67.6%) or laparotomic myomectomy were randomized (2:1) to Hydrogel (sprayed over surgically treated areas prior to wound closure, n = 48) or to control (standard care, n = 23). Patients (38 Hydrogel, 20 control) returned 8-10 weeks later for a second look. Adhesions were graded using a modified American Fertility Society (mAFS) scoring method. The primary efficacy measure was the posterior uterus mAFS score. RESULTS: For Hydrogel and control patients, respectively, mean +/- SD mAFS scores were 0.5 +/- 1.4 and 0.0 +/- 0.0 at baseline, and 1.1 +/- 1.9 and 2.6 +/- 2.2 at the second look. Similarly, mean changes from baseline were 0.8 +/- 2.0 and 2.6 +/- 2.2 (P = 0.01); 95% confidence intervals for these mean changes were (0.16-1.44) and (1.64-3.56). Adverse events were reported by 9.6 and 17.4% of Hydrogel and control patients, respectively. No intra-abdominal infections or post-operative site infections were reported. CONCLUSIONS: This 71-patient study provides the first clinical evidence of the safety and efficacy of Hydrogel for the reduction of adhesions following myomectomy. The ClinicalTrials.gov Identifier is NCT00562471.

Uterine compression U-sutures in primary postpartum hemorrhage after Cesarean section: fertility preservation with a simple and effective technique.

BACKGROUND: Transmural uterine compression suturing methods are a fertility-preserving alternative in patients with atonic primary postpartum hemorrhage (PPPH), which does not respond to manual compression or drugs. This study evaluated the effectiveness of a modified U-suturing technique in effecting uterine compression in patients with PPPH after Cesarean section. METHODS: U-suture uterine compression was introduced at our hospital at the beginning of 2005. The medical records of patients with PPPH after Cesarean section who had undergone this treatment, and results of a follow-up and questionnaire were evaluated and our experience with this method was reviewed. RESULTS: Between January 2005 and September 2007, seven patients underwent uterine compression with U-sutures after PPPH. In all cases, treatment was successful, the hemorrhage was controlled and the uterus preserved. Normal menstruation patterns returned in the five patients who returned the questionnaire and no surgery related morbidities were noted at the follow-up examinations of six patients. The technique was simple to perform in an emergency situation. CONCLUSIONS: Uterine compression with U-sutures is a highly effective and straightforward emergency procedure which conserves the uterus in these patients.

Bovine caruncular epithelial cell line (BCEC-1) isolated from the placenta forms a functional epithelial barrier in a polarised cell culture model.

In the bovine synepitheliochorial placenta key sites of fetal-maternal interaction are placentomes consisting of maternal caruncles interdigitating with fetal cotyledons. The aim of this study was to establish an epithelial cell line from caruncles of pregnant cows and to develop a model to study restricted trophoblast invasion, pathogenesis of pregnancy associated diseases and pathways of infection and transport. Primary epithelial cells were isolated, successfully subcultured for 32 passages and cryopreserved at various stages. The cultures were termed bovine caruncular epithelial cell line-1 (BCEC-1). Cytokeratin, zonula occludens-1 protein and vimentin but neither alpha-smooth muscle actin nor desmin were detected by immunofluorescence performed every 5 (+/-1) passages. These results were confirmed by Western blotting. BCEC-1 were then cultured either without matrix or on fibronectin or collagen coated Transwell polyester membrane inserts, respectively, enabling separate access to the basal or apical epithelial compartments. Transmission and scanning electron microscopy of BCEC-1 revealed ultrastructural features also observed in vivo, such as apical microvilli and junctional complexes. Transepithelial electrical resistance (TEER) was measured regularly and revealed an increase with advancing confluence in all cultures. Cultures on coated inserts reached confluence and corresponding TEER-levels at an earlier stage. In addition, the cells were tested negative for bovine virus diarrhoea (BVD) virus, but were permissive for the virus. In conclusion, the BCEC-1 cell line retained characteristics of maternal caruncular epithelial cells as observed in vivo and in primary cell cultures and thus will be a highly useful tool for future studies of pathways of invasion, fetal-maternal communication, transport and infection.

Development of an in vitro model for bovine placentation: a comparison of the in vivo and in vitro expression of integrins and components of extracellular matrix in bovine placental cells.

BACKGROUND/AIMS: Interaction of trophoblastic integrins with the extracellular matrix plays a role in embryo implantation and trophoblast invasion. The phenomenon of restricted trophoblast invasion, observed in the bovine epitheliochorial placenta offers intriguing conditions to study invasive processes. The migration of bovine trophoblast giant cells is accompanied by the expression of specific integrins and corresponding extracellular matrix ligands. METHODS: Primary cultures of different cell populations from cow placentomes were established and characterized, and in vitro phenotypes were compared with in vivo conditions by immunofluorescence. RESULTS: Propagated epithelial cells were positive for cytokeratin and vimentin, while fibroblasts contained alpha-smooth muscle actin, desmin and vimentin. Epithelial cells coexpressed integrin subunits alpha(6) and beta(1) with laminin, and fibroblast cells were positive for alpha(v), beta(3), fibronectin and laminin. In contrast to cells in vivo, cultured epithelial cells secreted fibronectin, while collagen IV was not detected. The occurrence of integrin subunits was confirmed at mRNA level by RT-PCR. CONCLUSION: We have established cell cultures isolated from maternal and fetal components of bovine placentomes expressing typical cytoskeletal filaments and integrin receptors also present in their in vivo counterparts. These bovine placentomal cells provide a suitable in vitro model for the study of cell-cell interactions.

Validation of primary epitheloid cell cultures isolated from bovine placental caruncles and cotyledons.

In order to study feto-maternal interactions in the bovine synepitheliochorial placenta primary cell cultures of both placentomal components throughout pregnancy, namely caruncular epithelial cells and trophoblast cells were developed. The aim of this study was to validate and improve a method to culture caruncular epithelial cells and fetal trophoblast from manually separated placentomes. Prior to seeding the presence of fetal cells in caruncular samples and vice-versa could be demonstrated by the detection of the Y-chromosome via fluorescence in situ hybridization (FISH) provided the fetus was male. Epitheloid shaped cells present in both cultures (cotyledon and caruncle) were characterized on a morphological basis as well as by immunofluorescence and Western blot thereby detecting cytokeratin, zonula occludens-1 and vimentin but not alpha-smooth muscle actin and desmin. The absence of the Y-chromosome demonstrated the caruncular origin of epitheloid cells. In addition, a population of polygonally shaped cells derived from the cotyledon was propagated and displayed the same cytoskeletal characteristics as described above. The presence of the Y-chromosome confirmed the fetal origin of these cells and the lacking uptake of fluorescence conjugated low density lipoprotein, specific for endothelial cells, identified polygonally shaped cells as fetal trophoblast cells. In conclusion, the cross-contamination of maternal and fetal cells in manually separated placentomes should be considered in future experiments as it may lead to false positive results dependent on the sensitivity of the method applied. This study highlights the importance of an appropriate cell characterization and identification, especially when isolating primary cells.

Management of vulvar melanoma and review of the literature.

BACKGROUND: Vulvar melanoma represents a rare group of malignancies and is the second most common vulvar malignancy. Treatment options range from local excision of the tumor and sentinel lymph node dissection to radical resection involving en bloc vulvectomy and inguinofemoral lymphanedectomy. Vulvar melanomas have an overall poor prognosis, and there is lack of consensus in the published literature regarding treatment options. OBJECTIVE: To discuss the management of vulvar melanomas through review of the actual literature. METHODS: Identification of studies through computerized searches (January 2006) was conducted using MEDLINE (1966 to present), the Cochrane Central Register of Controlled Trials, the National Research Register and the Medical Research Council's Clinical Trials Register. The medical subject headings and text words used were: vulvar melanoma, malignant, management, case report, and therapy. The literature review was done over the past 36 years. RESULT: Results of these primary retrospective series have shown no improvement in the overall recovery or disease survival rates. CONCLUSION: Patients with malignant melanoma are often diagnosed at 70 years of age with multiple comorbidities. Less radical surgery presents a more realistic option for many patients without decreasing their survival rates. Surgery is still the gold standard of treatment and offers the best available treatment for controlling and potential curing of malignant melanomas. However, the whole concept of therapy should be tailored to meet the specific needs of individual patients.

Ovine placental eluate immunoglobulins recognise isologous and third party acid-treated trophoblast microvesicle antigens in vitro.

Placental microvesicles were prepared from ovine placentae and immunoglobulins eluted with 0.5 M glycine buffer pH 2.5. The ability of eluate immunoglobulins to re-associate with isologous (self) and third party acidified microvesicles was tested by ELISA. Ovine placental immunoglobulins re-associated with isologous and third party acidified microvesicles suggesting that at least 2 types of antigenic epitopes I and II maybe expressed on the ovine placentae. Type I antigens may be present on placentae of all ovines while type II epitopes may be paternally derived, hence unique to each pregnancy. Analysis by SDS PAGE revealed the heavy and light chains of IgG at 57 and 27 kDa, respectively, together giving a relative molecular weight of 158 kDa. Results suggest that immunoglobulins produced to placental microvesicle antigens may be directed to some but not all antigenic epitopes expressed on the trophoblast, possibly defining a mechanism by which the foetus evades maternal immunological rejection.

Immunoglobulin G bound to ovine placenta is eluted by surgical cannulation and acid perfusion in situ.

OBJECTIVE: To elute placental bound immunoglobulin G (IgG) in situ. DESIGN: Laboratory based experimentation. SETTING: Biological Sciences Department, The University of Newcastle Australia and the Department of Biochemistry, University of Nairobi, Kenya. SUBJECTS: Twelve pregnant ewes 10 to 15 days before the onset of natural parturition. RESULTS: Placental eluates were rich in IgG, and IgG2. The relative molecular weight of placental IgG was estimated at 158kDa by gel filtration chromatography. Analysis of eluate by SDS PAGE revealed the heavy and light chains of IgG at 57 and 27kDa respectively together giving a relative molecular weight of 168kDa. CONCLUSION: Placental bound IgG may be crucial in immunology of pregnancy and together with the cognate antigen thereof may be useful as models for the study of maternal-fetal interaction in human pregnancy and in the development of experimental immunotherapy to immunologically compromised pregnancies in humans and livestock.

Human placental immunoglobulins show unique re-association patterns with isologous and third party acid treated trophoblast microvesicles in vitro.

OBJECTIVE: To study re-association pattern of human placental eluate immunoglobulins with acid treated isologous and third party trophoblast derived placental microvesicles. DESIGN: Laboratory based experimentation. SETTING: Biological Sciences Department and Discipline for Reproductive Medicine University of Newcastle, Australia and the Department of Biochemistry, University of Nairobi, Kenya. RESULTS: Placental eluate immunoglobulins re-associated with isologous and third party acidified microvesicles in three distinct patterns. I: eluate immunoglobulins re-associated more strongly with isologous and third party acid treated placental microvesicles, II: eluate immunoglobulins re-associated strongly with isologous but weakly with third party acid treated placental microvesicles, III: eluate immunoglobulins did not show preferential re-association with isologous and third party acid treated placental microvesicles. CONCLUSION: Two types of antigenic epitopes I and II may be expressed on the human placentae. Type I antigens may be present on all human placentae while type II epitopes may be paternally derived hence unique to each pregnancy. Also, immunoglobulins produced to placental microvesicle antigens may be directed to some but not all antigenic epitopes expressed on the human placental trophoblast.

Rosette inhibition test: a multicentre investigation of early pregnancy factor in humans.

The rosette inhibition test for the detection of early pregnancy factor is described in detail. The extended methodology presented here represents the cumulative experience of three independent laboratories. Special reference is made to the effect on the assay of varying the conditions of rosette formation between lymphocytes and sheep red blood cells. Antilymphocyte sera prepared for use in the rosette inhibition test fell into three categories: (i) with no rosette inhibiting activity, (ii) with rosette inhibiting activity which is not affected by the presence of EPF, and (iii) rosette inhibiting activity which is significantly increased in the presence of EPF. To date, this third reaction has been found to be a specific indication of the presence in serum of early pregnancy factor.