DNA methylation of HOXA10 in eutopic and ectopic endometrium.

STUDY QUESTION: Does the methylation status of the promoter region of the HOXA10 gene differ in eutopic and ectopic endometrium? SUMMARY ANSWER: The eutopic endometrium in women with endometriosis is significantly more methylated when compared with controls. WHAT IS KNOWN ALREADY: Expression of the HOXA10 gene, which is important for successful implantation, is reduced in women affected by endometriosis. STUDY DESIGN, SIZE AND DURATION: A pilot study was carried out including 18 women admitted for surgery for endometriosis-related pain (cases) and 12 women admitted for surgery because of non-endometriotic disease (control). Sample collection and analysis were performed between November 2010 and July 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: Endometrial tissue (eutopic and ectopic) underwent sodium bisulfite DNA modification, PCR amplification of two regions of the HOXA10 promoter and pyrosequencing analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The eutopic endometrium of women with endometriosis was significantly more methylated compared with endometrium from the control group (sequence 1: 8.68% in cases and 6.25% in the control group: P = 0.037, sequence 2: 11.89% in cases and 9.25% in the control group: P = 0.032). The eutopic endometrium was significantly more methylated than the ectopic tissue in patients with endometriosis (mean difference -3.6 sequence 1: P = 0.001 and -6.0 sequence 2: P = 0.0001). LIMITATIONS, REASONS FOR CAUTION: The study had a limited sample size and the fertility status of the majority of patients in our study was unknown. WIDER IMPLICATIONS OF THE FINDINGS: Our data regarding methylation state of the ectopic tissues contribute to a better etiopathologic understanding of endometriosis. STUDY FUNDING/COMPETING INTERESTS: No external funding was either sought or obtained for this study. The authors have no conflicts of interests to declare.

Expression of adhesion, attachment and invasion markers in eutopic and ectopic endometrium: a link to the aetiology of endometriosis.

BACKGROUND: Cell properties, such as attachment, adhesion and invasion, are important for the normal function of the endometrium. However, it is believed that the same properties may also be involved in the development of gynaecological diseases, such as endometriosis. Endometrial cells, shed by retrograde menstruation, may have an aberrant expression of molecules involved in these functions, leading to endometriosis. Therefore, the aim of this study was to investigate the expression of proteins involved in adhesion, attachment and invasion in eutopic and ectopic endometrium. METHODS: Endometrial biopsy specimens were collected from healthy volunteers (controls: proliferative phase, n = 10; secretory phase, n = 15) and from endometriosis patients (proliferative phase: n = 9, secretory phase: n = 10). Biopsy specimens from endometriomas were also collected (proliferative phase: n = 9, secretory phase: n = 10). Expression of apolipoprotein E (ApoE), integrin ß-2 (ITGB2), integrin ß-7 (ITGB7), Laminin γ-1 (LAMC1), CD24 molecule (CD24) and junctional adhesion molecule-1 (JAM-1) was evaluated with real-time reverse transcriptase polymerase chain reaction and immunohistochemistry. RESULTS: The endometrium from controls and women with endometriosis expressed ApoE, ITGB2, ITGB7, LAMC1, CD24 and JAM-1. Gene expression of ApoE and JAM-1 was decreased in both proliferative and secretory phase in the endometrium from women with endometriosis compared with control endometrium. Also, mRNA expression of LAMC1 was reduced in the endometrium from endometriosis patients compared with controls in the proliferative phase. An altered gene expression of CD24 was seen between the endometrium from endometriosis patients and endometriomas in the secretory phase. The ITGB2 protein expression was altered in epithelia cells between the endometrium from healthy volunteers and endometriosis patients in the secretory phase. CONCLUSIONS: We have shown differential expression of adhesion, attachment and invasion proteins in proliferative and secretory endometrium from controls and endometriosis patients and in endometriomas. This study suggests that molecules with these properties may have a role in the anchoring of endometrial cells at ectopic sites, thus initiating the development of endometriosis.

Defective production of both leukemia inhibitory factor and type 2 T-helper cytokines by decidual T cells in unexplained recurrent abortions.

Leukemia inhibitory factor is essential for embryo implantation, and a shift from type 1 T-helper to type 2 T-helper response at the fetal-maternal interface may contribute to successful pregnancy. We show that LIF production is associated with type 2 T-helper cells, is upregulated by IL-4 and progesterone and is downregulated by IL-12, IFN-gamma and IFN-alpha. We also show a decreased production of LIF, IL-4 and IL-10 by decidual T cells of women with unexplained recurrent abortions in comparison with that of women with normal gestation. The defective production of LIF and/or type 2 T-helper cytokines may contribute to the development of unexplained recurrent abortions.

[Tamoxifen, endometrial cancer risk and liquid based cytology. A paradigmatic case]. / Tamoxifene, rischio oncologico endometriale e citologia in fase liquida. Un caso clinico paradigmatico.

Long-term users of tamoxifen (TMX) are at increased risk for developing endometrial cancer. Early diagnosis is mainly based on transvaginal scan (TVS) and hysteroscopy with endometrial biopsy. Nevertheless, TVS does not provide a definitive diagnosis in most cases, particularly due to its high false-positive rate. In addition TMX related changes, such as "pseudocistic" pattern, affect endoscopic evaluation of the endometrium and biopsy sampling (in particular blind procedures) frequently yields insufficient tissue for diagnosis. The cause of the high inadequacy rate of endometrial biopsies in women on TMX might be related to the increase in endometrial fibrous component. The present case emphasizes the main difficulties in surveillance and early diagnosis of endometrial pathologies in TMX users. Liquid-based endometrial cytology played a determinant role in the diagnostic pathway of this patient. We believe it could be used solely or in association with TVS leading to many advantages in the surveillance of women receiving TMX.

Comparison of the number of uterine myomas detected by in-office transvaginal ultrasonography removed by laparotomic myomectomy: preoperative work-up concerns.

PURPOSE OF INVESTIGATION: To assess the ability of detecting the number of uterine myomas by transvaginal ultrasonography (TVS) performed supporting the clinical examination of general gynecologists' office practice. METHODS: A retrospective comparison of the number of myomas revealed by preoperative in-office TVS and documented after laparotomic myomectomy was conducted in 110 consecutive premenopausal patients referred for surgery. RESULTS: The sensitivity of TVS in revealing the exact number of myomas was 59.4% in the whole series. In the subgroup of 88 patients with a preoperative diagnosis of three or fewer myomas TVS missed at least one myoma in 31 (35.2%) cases, achieving a 64.8% sensitivity. Among the 72 women diagnosed with one myoma at preoperative TVS, 19 (26.4%) resulted to have two or more myomas at the end of surgery, reaching a 73.6% sensitivity of TVS in revealing the exact number of myomas. CONCLUSIONS: In-office TVS reinforces the clinical diagnosis of uterine myomas but it often fails in the detection of their number, resulting in a poor preoperative characterization of patients. The fact that one myoma may be overlooked in one-third of patients theoretically eligible for laparoscopic conservative surgery may motivate the implementation of US diagnosis when laparoscopic myomectomy is considered.

Clinical utility of liquid-based cytology for the characterization and management of endometrial polyps in postmenopausal age.

The proper management of endometrial polyps still represents a clinical ongoing challenge, especially when they are asymptomatic and occasionally discovered. The aim of this study was to evaluate liquid-based endometrial cytology to manage endometrial polyps in postmenopausal age by its ability to exclude hidden premalignant and malignant changes within polyps. Three hundred fifty-nine consecutive postmenopausal patients who underwent hysteroscopic diagnosis of endometrial polyp over a 3-year period and who were scheduled for surgical removal within the three subsequent months were retrospectively evaluated. Histologic results after resection during operative hysteroscopy or during hysterectomy were compared with liquid-based cytology and endometrial biopsy obtained at the time of diagnostic hysteroscopy. Eight of 359 patients (2.2%) had malignant or premalignant polyps interpreted as benign finding at hysteroscopy. Unsatisfactory samples were higher for endometrial biopsy compared to liquid-based cytology in the whole series and in the subgroup of low-risk asymptomatic patients (P < 0.001). Endometrial biopsy and liquid-based cytology revealed a sensitivity of 62% and 87.5%, respectively and a 100% specificity. Considering the subgroup of low-risk asymptomatic patients, liquid-based cytology disclosed all the five pathologic lesions with a 100% sensitivity and specificity. In conclusion, liquid-based cytology proved to be a useful tool to establish the nature of endometrial polyps in postmenopausal patients. Complete removal of the lesion should be offered to all symptomatic patients and those with established risk factors for endometrial cancer. Conversely, a wait and see attitude should be considered in case of asymptomatic low-risk polyps with typical appearance on hysteroscopy and negative liquid-based cytology.

Diagnosis and treatment of endometriosis. A review.

The correct approach for endometriosis management is still unclear. This review explores recent data concerning diagnosis and treatment of endometriosis, trying to define guidelines for the most appropriate diagnostic approach and therapeutic regimen. At present, laparoscopy is still considered the gold standard in endometriosis diagnosis. The risks and the diagnostic limitations of laparoscopy and the inaccuracy of clinical examination justify the considerable efforts made to improve the diagnosis with imaging techniques. The therapeutic approach is still far from being defined as causal and focuses on management of clinical symptoms of the disease rather than on the disease itself. A first-line medical therapy should be tried in patients with pelvic pain not asking for a pregnancy. Surgical treatment is considered the best treatment for women with pain and or pelvic mass who wish to become pregnant in a short time. For infertile patients, medical therapy has a limited role. The 2 treatment options include surgery or in vitro fertilization (IVF). According to our results, it seems that correct management of infertile women with endometriosis is a combination of surgery and IVF in women who did not obtain post-surgery pregnancy spontaneously.

Clinical, ethical, and medical legal considerations on emergency contraception.

PURPOSE OF INVESTIGATION: To evaluate how many women required the so-called "emergency contraception" at our outpatient service and what the actual role is of this kind of pharmacological administration in interfering with ovulation and pregnancy, paying particular attention to the ethical and medico-legal aspects of this subject. METHODS: During the period from 1 December 1998 to 30 November 2003, emergency contraception was prescribed to a total of 1,160 women. With regard to the contraceptives used, in most cases (1,132, 97.6%) a combined oral estrogen-progestogen pill (ethinyloestradiol 0.05 mg plus levonorgestrel 0.25 mg) was prescribed; in some cases (20 patients, 1.8%) danazol (400 mg), in four women (0.3%) a progestin-only pill (levonorgestrel 0.75 mg), and in four other women (0.3%) an intrauterine device. RESULTS: It does not come out that there were any pregnancies in our study patients since none of them, who were told to come back for follow-up, were seen at our termination of pregnancy service or delivery room. CONCLUSION: The "Yuzpe regimen" of a combined oral estrogen-progestogen pill has been the most commonly used method for emergency contraception. A new method recently proposed, a progestin-only pill with levonorgestrel 0.75 mg, is having better results than the previous one, with a lower incidence of side-effects and higher efficacy. Moreover, the treatment with this method does not interfere in case of a pregnancy already being carried and cannot interrupt it.

Fetal and neonatal ovarian cysts: what's their real meaning?

PURPOSE OF INVESTIGATION: The management of fetal ovarian cysts is still controversial despite the improvement in prenatal diagnosis with ultrasonography. Some studies suggest an aggressive management, while others opt for a conservative one. The prognosis of the majority of congenital ovarian cysts is good since they have a benign origin. Sometimes, however, complications such as torsion or rupture can occur which often require surgical intervention after delivery. In this paper we report our experience and a brief review of the literature. METHODS: The authors report on 32 pregnant women in whom ultrasonography revealed the presence of an echo-rare or echo-free area in the fetal abdomen suggestive of an ovarian cyst. All women were followed-up during pregnancy with serial ultrasound examinations. Postnatal ultrasound controls confirmed the prenatal diagnosis in all cases. The diameters of the cysts ranged from 2.7 to 7.5 cm. RESULTS: In the 16 cases (50%) in which the cyst diameter was below 4 cm, periodic ultrasound examinations revealed a tendency towards spontaneous regression of the cysts. In the other 16 cases (50%) in which the cyst diameter exceeded 4 cm, cystectomy was necessary due to subsequent complications (torsion in 6 cases, 37.5%, and intracystic hemorrhage in the other 10, 62.5%). CONCLUSION: The most appropriate clinical approach in the management of benign feto-neonatal ovarian cysts is to adopt a wait-and-see policy, assessing the course of the condition by means of periodic ultrasound monitoring. Only when tumefactions measure more than 4 cm in diameter with attendant complications is surgical therapy indicated. Without complications, however, aspiration of the cystic contents is possible even in ovarian cysts exceeding 4 cm in diameter.

What degree of maternal metabolic control in women with type 1 diabetes is associated with normal body size and proportions in full-term infants?

OBJECTIVE: To assess what degree of maternal metabolic control in women with type 1 diabetes is associated with normal fetal growth and results in normal neonatal body proportions in a group of full-term infants. RESEARCH DESIGN AND METHODS: We investigated the anthropometric characteristics of 98 full-term singleton infants born to 98 Caucasian women with type 1 diabetes enrolled within 12 weeks of gestation. The type 1 diabetic mother-infant pairs were divided into three groups on the basis of the daily glucose levels reached during the second and third trimesters of pregnancy (group 1: 37 mother-infant pairs with an average daily glucose level during the second and third trimesters of < or =95 mg/dl; group 2: 37 mother-infant pairs with an average daily glucose level during the second trimester of >95 mg/dl and during the third trimester of < or =95 mg/dl; group 3: 24 mother-infant pairs with an average daily glucose level during the second and third trimesters of >95 mg/dl; control group: 1,415 Caucasian mother-infant pairs with full-term singleton pregnancies and normal glucose challenge test screened for gestational diabetes. RESULTS: Infants of diabetic mothers in group 1 were similar to those of the control group in birth weight and in other anthropometric parameters. In contrast, offspring of diabetic mothers of groups 2 and 3 showed an increased incidence of large-for-gestational-age infants, significantly greater means of ponderal index and thoracic circumferences, and significantly smaller cranial/thoracic circumference ratios with respect to the control group. CONCLUSIONS: The results of our study suggest that, in diabetic pregnancies, only overall daily glucose values < or =95 mg/dl throughout the second and third trimesters can avoid alterations in fetal growth.

A pregnancy in an acromegalic woman during bromocriptine treatment: effects on growth hormone and prolactin in the maternal, fetal, and amniotic compartments.

An unexpected 20-week-old pregnancy was found in a young acromegalic who had been treated with 10 mg bromocriptine/day for 10 months. The drug was continued throughout the period of gestation. No growth of the pituitary adenoma was noticed. The intrauterine development of the fetus was normal. Bromocriptine therapy had no discernible effect on the expected patterns of secretion of placental hormones, but inhibited completely the increase of PRL in the serum of the mother. Maternal plasma GH concentrations were very high in spite of the treatment and progressively declined after delivery. The plasma GH level was normal in the child, but PRL was very low at birth and increased in the following days. The expected high PRL concentration was found in the amniotic fluid. This case study suggests that bromocriptine crosses the human placenta and affects the fetal pituitary, maternal GH does not influence fetal or amniotic GH, and amniotic fluid PRL correlates poorly with either maternal or fetal blood levels and is not affected by bromocriptine.

Non-classic sHLA class I in human oocyte culture medium.

Soluble human leukocyte antigen (sHLA) class I molecules have been described in all human fluids. These molecules play a significant role in immune function. sHLA has been shown to produce tolerance and to induce apoptosis in cytotoxic alloreactive T cells. They are also present in the supernatant of many cultured cells. Similarly, non-classic HLA class I antigens in soluble form are present in human fluids. Among these, HLA-G is the most important because of its location in fetal tissue that suggests maternal immunological tolerance of the fetal semiallograft. In our present study we show that using two monoclonal antibodies, w6/32 and TP25.99, in the enzyme-linked immunosorbent assay allows the detection of non-classic sHLA class I molecules in the medium from human embryo cultures. The sample were collected from oocytes cultures. Oocyte donors were 11 women attending the in vitro fertilization program. The results showed a significant association (chi2 = 9.66, p = 0.002) between sHLA antigens and the oocyte cleavage rate measured 48 h after fertilization.

Risk factors for fetal macrosomia: the importance of a positive oral glucose challenge test.

OBJECTIVE: The aim of this study was to investigate whether minor abnormalities of glucose metabolism without gestational diabetes are a risk factor for fetal overgrowth. DESIGN: A sample of 1883 unselected white mother-infant pairs were screened for gestational diabetes using a 50 g 1-h oral glucose challenge test (GCT) in two periods of pregnancy: early (16-20 weeks) and late (26-30 weeks). METHODS: The effects of risk factors (glucose metabolism, previous history of mothers, obesity, multiparity and age of mothers) were estimated using a multinomial logit model. RESULTS: The level of risk was related to gestational age at the appearance of an abnormal GCT. Patients with an abnormal GCT in the early and late periods of pregnancy (Group 1) had a risk of delivering a large for gestational age (LGA) infant seven times higher than the control group (normal GCT in both periods), and patients with a normal GCT in the early period and an abnormal GCT in the late period (Group 2) showed a risk three times higher than the control group. Among the historical risk factors for LGA infants, such as maternal obesity, multiparity, previous gestational diabetes and previous delivery of an infant weighing 4000 g or more, only the latter was associated with fetal overgrowth with a risk level 4.7 higher than the control group. Group 1 patients had a significantly higher incidence of pregnancy-induced hypertension and preterm birth. There were no differences in the frequency of 5-min Apgar score < 7 and metabolic complications among the infants of all groups. We found a significantly higher rate of shoulder dystocia in Group 1 infants than in infants in the other groups. CONCLUSIONS: Our results suggest that a positive GCT at 26-30 weeks is the most important risk factor for fetal overgrowth. This result was strongly enforced in patients who had also shown a positive early GCT at 16-20 weeks.

Can hysteroscopic evaluation of endometrial carcinoma influence therapeutic treatment?

235 cases of primary endometrial adenocarcinoma (AC) (age range, 37-94; mean age, 61 years) were collected during the period 1980-1992. Hysteroscopic examination of both the endometrial cavity and the cervical canal was performed in every patient prior to hysterectomy, and evaluations of cancer extension in the endometrium (focal: 97 pts; partial: 82 pts; massive: 47 pts; unevaluable: 9 pts) and of endocervical involvement (positive: 45 pts) were compared to the histological findings and survival rates. The chi 2 test was used for statistical analysis, and statistical significance was considered where the p value was < 0.05. Endometrial extension was poorly related to the depth of myometrial invasion (M1 = depth of invasion to < 1/2 myometrium, M2 = invasion to > 1/2 myometrium): focal AC: M1 57.8%, M2 42.2%; partial AC: M1 40.2%, M2 59.8%; massive AC: M1 51.1%, M2 48.9%; (p = 0.5). Endocervical involvement was unrelated to endometrial extension. No correlation was found between AC histological grade (G1-G3) and entity of endometrial extension, whereas grade showed a significant correlation with myometrial invasion (G1 M1: 69.1%; G3 M1: 41.0%; p = 0.002) and survival rates (G1 90.4%, G2 88.5%, G3 69.4%; p = 0.01). Five-year survival figures showed no evident correlation with cancer extension (focal AC: 86.5%; partial AC: 87.8%; massive AC: 86.3%; p = 0.9) whereas myometrial invasion showed a statistical significance (M1: 91.4%, M2: 79.7%; p = 0.03). Three patterns of invasion were defined: pushing (P), infiltrative (I) and diffuse (D) isolated cells. There were significant differences between the various growth patterns and survival rates (P 90.7%; I 84.3%; D 45.4%; p = 0.0001). False negative rate of the hysteroscopic diagnosis of cervical involvement was 7.9% (18 cases); however, in 6 of these cases only deep cervical invasion was found.

Pressure lavage under ultrasound guidance: a new approach for outpatient treatment of intrauterine adhesions.

OBJECTIVE: To present pressure lavage under ultrasound guidance (PLUG) as a new therapeutic procedure for selected cases of intrauterine adhesions (IUA). DESIGN: An open clinical investigation with no control group. SETTING: Teaching hospital. PATIENT(S): Seven consecutive patients referred to our department for secondary amenorrhea due to IUA. INTERVENTION(S): A newly developed technique based on sonohysterography was used to monitor the effects of intrauterine injections of saline solution on the continuous accumulation of saline in the uterine cavity for the mechanical disruption of IUA. MAIN OUTCOME MEASURE(S): Lysis of intrauterine adhesions, restoration of menses, and increased pregnancy rate in infertile patients. RESULT(S): Five patients with mild IUA obtained satisfactory lysis of adhesions by the use of the PLUG technique. A second-look hysteroscopy after 1 month showed that filmy adhesions persisted in two patients with moderate IUA. These adhesions were removed successfully during hysteroscopy. Restoration of menses was obtained and has continued in all patients. Two of the three infertile patients became pregnant. CONCLUSION(S): This technique is safe and ideal as an in-office procedure. PLUG allows complete lysis in mild IUA cases, and the need for therapeutic, and possibly follow-up hysteroscopy, can be avoided. In moderate IUA cases, the procedure may represent a useful initial step in reducing the need for operative hysteroscopy.

Time course of recovery and complications of HELLP syndrome with two different treatments: heparin or dexamethasone.

HELLP syndrome is a severe complication of pregnancy characterized by microangiopathic hemolytic anemia, hepatic dysfunction and thrombocytopenia. Though delivery is the ultimate therapeutic option, medical treatments, including the use of heparin or corticosteroids, have been employed in the attempt to improve maternal prognosis. The aim of this retrospective study was to compare the time course of recovery and the incidence of complications in women with HELLP syndrome receiving either heparin or dexamethasone. Between January 1990 and December 1998, 32 patients with HELLP syndrome were cared for at the Institute of Obstetrics and Gynecology of the University of Florence: 20 patients were treated with heparin, administered subcutaneously at a dose of 5000 IU every 12 h, whereas 12 women received dexamethasone, administered intravenously at a dose of 10 mg every 12 h. Categorical data were evaluated with chi-square and Fisher's exact test; continuous data were analyzed with Mann-Whitney U test; P < .05 was considered significant. In the subgroup treated with heparin the incidence of disseminated intravascular coagulation (DIC) (P < .02), the number of patients requiring blood transfusion (P < .05) and the length of stay at the Intensive Care Unit (ICU) (P < .04) were significantly increased as compared with the subgroup receiving dexamethasone; in this latter subgroup, significantly higher platelet count and hematocrit values, and significantly lower levels of lactate dehydrogenase (LDH) could be documented starting from day 2 after delivery. The results of our investigation suggest that the use of dexamethasone in patients with HELLP syndrome is associated with faster regression and lower incidence of complications in comparison to heparin.

Analysis of the action of corticosteroid treatment in immunologic infertility: a preliminary report and an alternative hypothesis.

The presence of sperm antibodies can be demonstrated in 8-10% of the male partners of infertile couples. The therapeutic schedule with which the highest pregnancy rate has been obtained in these cases is that proposed by Shulman, which uses methylprednisolone (MP). If treatment with corticosteroids (CS) is effective, the way in which it acts is not entirely clear. In this study we report the results of 16 treatment cycles with CS administered to eight male patients having sperm antibodies in their serum, in which several parameters of humoral immunity were evaluated. The results are conflicting: several parameters (such as IgG concentration) underwent only slight variations after 7 days of therapy, whereas in 12 cycles out of 16, the Tray agglutination test (TAT) indicated that a reduction or disappearance of the antibodies had been obtained. This confirms the usefulness of CS in immunological infertility, and allows us to hypothesize that the beneficial effect may be found in a reduction of inflammation rather than in a suppression of the immunological response, since CS are well known to have these two kinds of effect.

Fertilisation and implantation failure in an oral contraceptive user.

We report the case of a young woman taking a low-dose oral contraceptive (gestodene 0.075mg and ethinylestradiol 0.02mg) in whom we documented by both hormonal assays and sonographic evaluations the occurrence of ovulation, oocyte fertilization and embryo implantation. However, the implantation process did not complete and only a biochemical pregnancy was registered. On the basis of known actions of estroprogestin on endometrium that are not conducive to implantation, it is possible that the pregnancy loss was originated by oral contraceptive's hormonal influence at endometrial level.

I. Aging of the human endometrium: a basic morphological and immunohistochemical study.

OBJECTIVE: To evaluate if human endometrium presents morphological variations suggestive of an age-related decline in endometrial receptivity. STUDY DESIGN: Peri-implantation endometrium of younger (<30 years of age: n = 13) and older (>40 years of age: n = 17) normally menstruating women was studied. Endometrial specimens were routinely fixed in buffered formalin and embedded in paraffin. Sections (5 mu m) were stained with hematoxylin-eosin, periodic acid-Schiff (PAS) and Trichrome conforming to Masson according to conventional histologic examination. Several consecutive sections were used for the following immunohistochemical study: vascular localization (CD34), cellular proliferation index (PCNA), progesterone and estrogen receptors. RESULTS: Using both the traditional morphological evaluation and monoclonal antibodies, no significant differences were found between the endometria of women <30 years of age and those of women >40. CONCLUSIONS: Our results suggest that human endometrium does not age, at least while cyclic hormonal stimulation and menstruation are present.

Hormonal patterns, steroid receptors and morphological pictures of endometrium in hyperstimulated IVF cycles.

OBJECTIVE: The purpose of this contribution is to investigate the pathophysiology of the abnormal endometrial development in hyperstimulated IVF cycles. STUDY DESIGN: In 12 IVF-patients who did not have embryo transfer because of failure of oocyte fertilization, serum values of 17 beta-estradiol, progesterone, FSH, LH, total and free testosterone, and androstenedione were measured on the pick-up day and were evaluated with respect to the values normally expressed in the day of ovulation; in the endometrial specimens collected 2 days later, at the time of embryo replacement, estrogen and progesterone receptors were immunohistochemically determined and dating by the Noyes method was performed. RESULTS: 17 beta-Estradiol values are constantly higher, and progesterone levels are, only in four cases, higher than expected for the day of ovulation in a natural cycle. These hormonal patterns can only partially explain the pattern of steroid receptors: progesterone receptors are expressed sparsely both in glands and stroma, while estrogen receptors are abundant in the glands and absent in the stroma. In 11 of 12 patients an abnormal endometrial development with stromal advancement was observed: this morphological picture of the endometrium could partially be explained only in the four cases presenting high progesterone levels by serum values and endometrial receptor content of estrogen and progesterone. CONCLUSIONS: The abnormal endometrial development in hyperstimulated IVF cycles could only in part be explained by estrogen and progesterone, and other factors have to be considered.