Assessment of levator hiatal area using 3D/4D transperineal ultrasound in women with deep infiltrating endometriosis and superficial dyspareunia treated with pelvic floor muscle physiotherapy: randomized controlled trial.

OBJECTIVES: Deep infiltrating endometriosis (DIE) is associated with chronic pelvic pain, dyspareunia and pelvic floor muscle hypertonia. The primary aim of this study was to evaluate the effect of pelvic floor physiotherapy (PFP) on the area of levator ani hiatus during Valsalva maneuver, assessed using transperineal ultrasound, in women with DIE suffering from superficial dyspareunia. METHODS: This was a randomized controlled trial of 34 nulliparous women diagnosed with DIE and associated superficial dyspareunia. After an initial clinical examination, all patients underwent three-dimensional/four-dimensional (3D/4D) transperineal ultrasound to measure the levator hiatal area (LHA) at rest, on maximum pelvic floor muscle contraction and on maximum Valsalva maneuver, and were asked to rate their pain symptoms using a numerical rating scale (NRS). Eligible women were assigned randomly (1:1 ratio) to no intervention (control group, 17 women) or treatment with five individual sessions of PFP (study group, 17 women). Four months after the first examination, all women underwent a second evaluation of pain symptoms and LHA on transperineal ultrasound. The primary outcome measure was the percentage change in LHA on maximum Valsalva maneuver between the baseline and follow-up examinations. The percentage changes in pain symptoms between the two examinations, including superficial and deep dyspareunia, dysmenorrhea, chronic pelvic pain, dysuria and dyschezia, were also evaluated. RESULTS: Thirty women, comprising 17 in the study group and 13 in the control group, completed the study and were included in the analysis. The percentage change in LHA on maximum Valsalva maneuver between the two examinations was higher in the study group than in the control group (20.0 ± 24.8% vs -0.5 ± 3.3%; P = 0.02), indicating better pelvic floor muscle relaxation. After PFP treatment, the NRS score for superficial dyspareunia remained almost unchanged in the control group (median change in NRS (Δ-NRS), 0 (interquartile range (IQR), 0-0)) while a marked reduction was observed in the study group (median Δ-NRS, -3 (IQR, -4 to -2); P < 0.01). Moreover, there was a significant difference between the PFP and control groups with regards to the change in chronic pelvic pain (median Δ-NRS, 0 (IQR, -2 to 0) vs 0 (IQR, 0-1); P = 0.01). CONCLUSIONS: In women with DIE, PFP seems to result in increased LHA on Valsalva maneuver, as observed by 3D/4D transperineal ultrasound, leading to improved superficial dyspareunia, chronic pelvic pain and pelvic floor muscle relaxation. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Successful achievement after heterotopic transplantations of long-term stored ovarian tissue in Hodgkin's lymphoma survivor.

In this case report, we describe the outcomes of two heterotopic transplantations of cryopreserved ovarian tissue performed in a patient with HL, after 11 and 15 years of storage. At the age of 30, the patient underwent laparoscopy to collect ovarian tissue for cryopreservation before chemotherapy and radiotherapy. Eleven years later she experienced premature ovarian failure (POF). As the patient was only interested in endocrine function recovery, two heterotopic ovarian tissue transplantations were performed in the abdominal wall above the rectus muscle respectively 11 and 15 years after cryopreservation. Before transplantation, ovarian samples were analyzed to assess neoplastic contamination and tissue quality. The analysis on thawed ovarian tissue did not reveal micrometastasis and it showed well-preserved follicles and stroma. After both ovarian tissue grafting, menopausal symptoms ceased. The patient had periods approximately every 30-days and hormonal levels were within the premenopausal range. The endocrine function lasted 3-years after the first heterotopic transplantation and is still ongoing after second transplantation. Cryopreservation of ovarian tissue should be proposed to HL patients, as the incidence of POF as a long-term complication is not negligible. In these patients heterotopic transplantation is a useful tool to eliminate menopausal symptoms, preventing osteoporosis and reducing cardiovascular risks.

Pelvic floor muscle dysfunction on 3D/4D transperineal ultrasound in patients with deep infiltrating endometriosis: a pilot study.

OBJECTIVE: Pelvic floor muscle (PFM) dysfunction seems to play an important role in the pathophysiology of pelvic pain, including that associated with deep infiltrating endometriosis (DIE). The aim of this study was to evaluate the static and dynamic morphometry of the PFM using three-dimensional (3D) and four-dimensional (4D) transperineal ultrasound in women with DIE compared with asymptomatic healthy women. METHODS: This was a pilot, prospective study conducted at our tertiary center between March and November 2015. Fifty nulliparous women with DIE (study group) and 35 nulliparous asymptomatic healthy women (control group) were included. 3D/4D transperineal ultrasound examination of the PFM was performed in both groups. Levator hiatal area (LHA) and anteroposterior and left-right transverse diameters were evaluated at rest, on maximum PFM contraction and on maximum Valsalva maneuver. Persistent levator ani muscle (LAM) coactivation during Valsalva maneuver was investigated. RESULTS: Compared with the control group, women with DIE had a smaller LHA at rest (P = 0.03) and during Valsalva maneuver (P < 0.01). Furthermore, reduction in LHA during PFM contraction (P < 0.001) and enlargement in LHA during Valsalva maneuver (P = 0.01) were significantly less marked. In comparison with controls, women with DIE presented a higher frequency of LAM coactivation during Valsalva maneuver, although this difference did not reach statistical significance (P = 0.05). CONCLUSIONS: 3D and 4D transperineal ultrasound is an objective and non-invasive method for PFM morphometry and may have a role in detecting PFM dysfunction in women with DIE. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Pelvic myeloid sarcoma: a multidisciplinary approach.

Myeloid sarcoma (MS) is a rare tumor mass derived from the extramedullary proliferation of blasts of one or more of myeloid lineages. It usually occurs at an anatomical site other than the bone marrow (BM). Among the anatomical site which may be involved, female genital tract is a rare localization. When MS follows a previous history of myeloid pathology it is usually associated to a poor prognosis. To date this disease was managed with exploratory laparotomy or with surgical debulking. The authors report a case of laparosc6pic diagnosis of a pelvic myeloid sarcoma in a patient previously affected by acute mycloid leukemia, evidencing the importance of minimally invasive diagnosis and subsequent multidisciplinary management.

Morphological, ultrastructural and functional imaging of frozen/thawed and vitrified/warmed human ovarian tissue retrieved from oncological patients.

STUDY QUESTION: Which is the best method for human ovarian tissue cryopreservation: slow freezing/rapid thawing (SF/RT) or vitrification/warming (V/W)? SUMMARY ANSWER: The conventional SF/RT protocol used in this study seems to better preserve the morpho-functional status of human cryopreserved ovarian tissue than the used open carrier V/W protocol. WHAT IS KNOWN ALREADY: Cryopreservation of human ovarian tissue is generally performed using the SF/RT method. However, reduction in the follicular pool and stroma damage are often observed. An emerging alternative procedure is represented by V/W which seems to allow the maintenance of the morphological integrity of the stroma. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study including six patients affected by oncological diseases and enrolled from January to December 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian tissue was laparoscopically harvested from the right and left ovaries and was cryopreserved using a routinary SF/RT protocol or a V/W method, involving tissue incubation in two solutions (containing propylene glycol, ethylene glycol and sucrose at different concentrations) and vitrification in an open system. For each patient, three pieces from each ovary were collected at the time of laparoscopy (fresh tissue) and after storage (SF/RT or V/W) and processed for light microscopy (LM) and transmission electron microscopy (TEM), to assess the morphological and ultrastructural features of follicles and stroma, and for laser scanning confocal microscopy (LSCM), to determine the functional energetic/redox stroma status. The preservation status of SF/RT and V/W ovarian tissues was compared with that of fresh ones, as well as between them. MAIN RESULTS AND THE ROLE OF CHANCE: By LM and TEM, SF/RT and V/W samples showed cryodamage of small entity. Interstitial oedema and increased stromal cell vacuolization and chromatin clumping were observed in SF/RT samples; in contrast, V/W samples showed oocyte nuclei with slightly thickened chromatin and irregular shapes. The functional imaging analysis by LSCM revealed that the mitochondrial activity and intracellular reactive oxygen species levels were reduced both in SF/RT and in V/W samples compared with fresh samples. The study also showed progressive dysfunction of the mitochondrial activity going from the outer to the inner serial section of the ovarian cortex. The reduction of mitochondrial activity of V/W samples compared with fresh samples was significantly higher in the inner section than in the outer section. LIMITATIONS, REASONS FOR CAUTION: The results report the bioenergetic and oxidative status assessment of fresh and cryopreserved human ovarian tissue by LSCM, a technique recently applied to tissue samples. The use of LSCM on human ovarian tissues after SF/RT or V/W is a new application that requires validation. The procedures for mitochondrial staining with functional probes and fixing are not yet standardized. Xenografting of the cryopreserved ovarian tissue in severe combined immunodeficient mice and in vitro culture have not yet been performed. WIDER IMPLICATIONS OF THE FINDINGS: The identification of a cryopreservation method able to maintain the morpho-functional integrity of the ovarian tissue and a number of follicles comparable with those observed in fresh tissue might optimize results in clinical practice, in terms of recovery, duration of ovarian function and increased delivery outcomes after replanting. The SF/RT protocol allowed better morpho-functional tissue integrity than the V/W procedure. STUDY FUNDING/COMPETING INTERESTS: Funding was provided by Fondazione del Monte di Bologna e Ravenna, Italy. Dr N.A.M. was granted by the project ONEV MIUR PONa3 00134-n.254/R&C 18 5 2011 and the project GR-2011-02351396 (Ministry of Health, Young Researchers Grant 2011/2012). There are no competing interests. TRIAL REGISTRATION NUMBER: Clinical trial 74/2001/0 (approved:13 2 2002): 'Pilot study on cryopreservation of human ovarian tissue: morphological and immunohistochemical analysis before and after cryopreservation'.

Histological evaluation of ureteral involvement in women with deep infiltrating endometriosis: analysis of a large series.

STUDY QUESTION: In women with deeply infiltrating endometriosis (DIE) what is the prevalence of involvement of endometriotic tissue and fibrosis in ureteral endometriosis (UE), as assessed by histological staining? SUMMARY ANSWER: In women with DIE, ureteral involvement is more often due to endometriotic tissue rather than fibrosis. WHAT IS KNOWN ALREADY: In the current literature, histological evaluation of ureteral endometriosis is mainly based on the degree of wall infiltration by endometriosis instead of the tissue composition. A few studies reported ill-defined and contradictory histological data on the tissue composition of UE. STUDY DESIGN, SIZE, DURATION: Retrospective observational study based on clinical records of women affected by DIE, laparoscopically treated for UE at a tertiary referral center, between January 2010 and March 2013. All cases of ureteral nodule excision or ureterectomy with histological examination of the specimens were included. Exclusion criteria were other identified causes of hydroureteronephrosis, medical therapy for a period of at least 3 months before surgery and previous surgery for DIE. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 77 patients were included in the study and among them seven (9%) presented with bilateral ureteral involvement, giving a total of 84 cases of UE available for analysis. All patients had stage IV endometriosis. According, respectively, to the presence of endometrial glands and/or stroma cells or of fibrotic tissue only, the endometriotic UE and fibrotic UE groups were compared with regard to hydroureteronephrosis at pre-operative urinary tract computerized tomography scan, type of surgical procedure performed to treat UE (nodule removal or ureterectomy), association with other locations of the disease and post-operative complications (ureteral fistula or stenosis). MAIN RESULTS AND THE ROLE OF CHANCE: For the 84 cases of UE, 65 (77%) and 19 (23%), respectively, showed endometriotic tissue and fibrotic tissue only. Presence of hydroureteronephrosis and endometriotic pattern of UE showed a significant association [endometriotic UE 44/65 (68%) versus fibrotic UE 8/19 (42%); P = 0.04]. Fibrotic pattern of UE and presence of concomitant recto-vaginal endometriosis showed a significant association [endometriotic group: 29/65 (45%) versus fibrotic group 18/19 (95%); P < 0.001]. LIMITATIONS, REASONS FOR CAUTION: The retrospective and monocentric (tertiary referral center) study design. WIDER IMPLICATIONS OF THE FINDINGS: Besides the distinction between extrinsic and intrinsic UE based on the degree of wall infiltration by endometriosis, a new classification according to the histological pattern of UE could be useful for clinicians, both in the diagnostic and therapeutic fields. STUDY FUNDING/COMPETING INTERESTS: None.

Evidence for a stimulatory role of high doses of recombinant human follicle-stimulating hormone in the treatment of male-factor infertility.

The efficacy of recombinant human follicle-stimulating hormone (rhFSH) in the treatment of normogonadotropic patients with male-factor infertility was assessed. Forty-five infertile men with moderate/severe oligoasthenozoospermia and normal FSH, luteinizing hormone (LH) and testosterone (T) levels were treated with high rhFSH dose (300 IU) on alternate days for ≥4 months. In all, the seminal parameters, endocrine profile (FSH, LH, prolactin (PRL), total and free T and estradiol) and pregnancy rate were evaluated before, during and after rhFSH treatment. Fifteen infertile men were treated with placebo and studied in the same way, as control group. rhFSH treatment induced a marked increase in sperm count and no change in sperm motility, morphology and viability. No changes in seminal parameters were observed in the placebo group. FSH levels increased during treatment with rhFSH and not with placebo. No variations in LH, PRL, free and total T and estradiol were evidenced during treatment. A significant pregnancy rate in rhFSH versus placebo patients was also highlighted. Prolonged treatment with high rhFSH doses leads to increase sperm count and improve the spontaneous pregnancy rate in normogonadotropic infertile patients with oligoasthenozoospermia. rhFSH may represent a rational and useful tool in the treatment of male-factor infertility.

Segmental bowel resection for colorectal endometriosis: is there a correlation between histological pattern and clinical outcomes?

BACKGROUND: Laparoscopic segmental resection as a treatment for intestinal endometriosis can be supported by favorable clinical outcomes, but carries a high risk of major complications. The purpose of this study is to evaluate histopathological patterns of colorectal endometriosis and investigate potential relationships between histological findings and clinical data. METHODS: We consecutively included 47 patients treated with laparoscopic segmental resection because of symptomatic colorectal endometriosis. All patients underwent follow-up for a median of 18 months (range: 6-35). We examined the histological patterns of colorectal endometriosis and evaluated the relationships between histological findings (satellite lesions, positive margins and vertical infiltration) and clinical outcomes (incidence of recurrence, quality of life and symptom improvement). Moreover, we observed if satellite lesions could influence preoperative scores of the short form-36 health survey (SF-36) questionnaire and visual analogue score (VAS) for pain symptoms. RESULTS: There were no statistically significant differences in terms of anatomical and pain recurrences, pain symptoms and quality of life improvement among patients with or without positive margins, satellite lesions and different degrees of vertical infiltration (P > 0.05). Furthermore, women with or without satellite lesions were no different in terms of preoperative VAS of pain symptoms and SF-36 scores (P > 0.05). CONCLUSIONS: The presence of satellite lesions or positive resection margins does not seem to influence clinical outcomes of segmental colorectal resection. Similarly, satellite lesions do not appear to have a major role in determining preoperative clinical presentation. These results may be useful to reconsider the surgical strategy for bowel endometriosis.

Doppler flow analysis of the palmaris superficial branch of the radial artery in postmenopausal women with acroparesthesia: the role of hormone therapy. A pilot study.

METHOD: Twenty-three patients with acroparesthesia were submitted to clinical evaluation and color Doppler analysis of the uterine artery and palmaris superficial branch of the radial artery. Thirteen women (Group I) were submitted to hormone treatment with drospirenone 2 mg + estradiol emidrate 1 mg. Ten patients refused the treatment and served as controls (Group II). The patients were studied at baseline and after 6 months' therapy. RESULTS: After 6 months of hormone therapy, the resistances of the uterine artery and palmaris superficial branch of the radial artery significantly decreased in Group I patients. This was associated with the complete disappearance of paresthesic symptoms in 12/13 (92%) of the treated patients. In patients belonging to Group II, the paresthesia remained unchanged. CONCLUSION: Hormone therapy with drospirenone may increase the forearm/hand blood flow, and favor the amelioration of paresthesia.

Diagnosis and treatment of uncommon ileal endometriosis: a case report and literature review.

Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. It is a common finding in premenopausal women and commonly affects the gastrointestinal tract, especially the rectosigmoid tract. Small bowel involvement is rare and usually asymptomatic making diagnosis difficult. Here we report an uncommon case of exophytic ileal endometriosis surgically treated. Detailed pre-operative counselling on the risk of ileal surgery should always be considered in all cases with endometriosis requiring surgery. We also present a review of the literature regarding the clinical presentation, diagnosis, and treatment of this challenging condition.

Preservation of ovarian function.

In the last years, advances in diagnosis and new treatments of cancer patient have increased the life expectancy of children, adolescent and women with cancer. Unfortunately, the ovaries are very sensitive to chemio-radiotherapy that may induce the loss of ovarian function and fertility with consequent premature ovarian failure. The different cryopreservation options available for fertility preservation in cancer patients are embryo cryopreservation, oocyte cryopreservation and ovarian tissue cryopreservation. The choice depends on different parameters: the type and timing of cancer treatment, the type of disease, the patient's age. The advances in reproductive technology have made fertility preservation a real possibility for patients whether they are girls or young women whose gonadal function is threatened by natural premature menopause, or by cancer therapy or surgical sterilisation.

Effects of indoor air purification by an air cleaning system (Koala technology) on semen parameters in male factor infertility: results of a pilot study.

A number of studies indicated a clear decline in semen quality in the past 30-50 years and there is accumulating evidence that this decline might result from exposure to high levels of air pollution. To examine the impact of environment on male reproductive ability, we undertook for the first time a pilot study on semen quality of infertile men exposed to purification of indoor air. Ten subjects with a history of unexplained male infertility and poor semen quality were exposed for at least 1 year to a cleaning indoor air system (Koala technology). The key feature of this air purifier is the unique innovative multiple filtering system. The treatment of total purification of indoor air showed neither improvements in semen parameters nor variation in reproductive hormones (P = N.S.), but induced an evident increase (P < 0.03 and more) in seminal leucocytic concentrations. Within the limits due to the small sample of subjects recruited, the sole purification of indoor air does not seem enough to improve semen quality, although the increase in leucocytic concentrations could indicate an activation of the role of immunosurveillance in a purified indoor air environment.

Epigallocatechin-3-gallate inhibits doxorubicin-induced inflammation on human ovarian tissue.

Chemotherapy protocol can destroy the reproductive potential of young cancer patients. Doxorubicin (DOX) is a potent anthracycline commonly used in the treatment of numerous malignancies. The purpose of the study was to evaluate the ovarian toxicity of DOX via inflammation and the possible protective effect of the green tea polyphenol epigallocatechin-3-gallate (EGCG). Ovarian tissue of three patients was cultured with 1 µg/ml DOX and/or 10 µg/ml EGCG for 24 and 48 h. Levels of inflammatory factors were determined by quantitative Real-Time PCR, western blot, zimography, and multiplex bead-based immunoassay. Morphological evaluation, damaged follicle count and TUNEL assay were also performed. DOX influenced inflammatory responses by inducing a significant increase in the expression of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and cyclooxigenase-2 (COX-2), of inflammatory interleukins (IL), such as interleukin-6 (IL-6) and interleukin-8 (IL-8), and the inflammatory proteins mediators metalloproteinase-2 and metalloproteinase-9 (MMP2 and MMP9). IL-8 secretion in the culture supernatants and MMP9 activity also significantly raised after DOX treatment. Moreover, a histological evaluation of the ovarian tissue showed morphological damage to follicles and stroma after DOX exposure. EGCG significantly reduced DOX-induced inflammatory responses and improved the preservation of follicles. DOX-induced inflammation could be responsible for the ovarian function impairment of chemotherapy. EGCG could have a protective role in reducing DOX-mediated inflammatory responses in human ovarian tissue.

Healthy twins delivered after oocyte cryopreservation and bilateral ovariectomy for ovarian cancer.

Anti-neoplastic treatments have significantly increased the survival of cancer patients, but female patients risk premature menopause. Oocyte cryopreservation has been proposed as a fertility-saving option. This report describes the first live birth achieved with autologous cryopreserved oocytes in an ovariectomized borderline cancer patient. A patient with a borderline ovarian tumour asked for oocyte cryopreservation after a right adnexectomy. Ovulation induction resulted in the retrieval and cryopreservation of seven mature oocytes. Thirty-nine months after a left ovariectomy, the patient asked for oocyte thawing and embryo transfer. Endometrial growth was induced using hormone replacement treatment. Three of the seven cryopreserved oocytes were thawed; they survived and, after insemination, normal fertilization took place. Three embryos were transferred into the patient's uterus. A twin pregnancy was achieved with the birth of two healthy females. Oocyte cryopreservation may be a reliable option for preserving fertility in young cancer patients who risk premature menopause due to surgery, chemotherapy or radiotherapy.

High concentrations of catecholamines in human hypothalamic-hypophysial blood.

While the hypothalamic-hypophysial portal system has been extensively studied in laboratory animals, equivalent studies have not been performed in humans. Here, we present an experimental procedure for collecting suprapituitary blood in man. To solve the question on the origin of such blood we investigated specific markers of hypothalamic secretory activity: the catecholamines (CAs). We found (a) norepinephrine (NE), dopamine (DA), and epinephrine (E) concentrations from approximately 1.5 to 2.5, 3.5 to 4.5, and 6- to 10-fold higher, respectively, in suprapituitary than peripheral blood, (b) different NE/DA and NE/E ratios in favor of DA and E in suprapituitary blood, and (c), a complete (100%) group separation (suprapituitary vs. peripheral) when discriminant analysis included only DA and E. These data indicate that suprapituitary blood composition is different from that of the peripheral blood, and is particularly rich in CAs and claimed differences between DA and E release on one hand and NE release on the other in suprapituitary blood also are observed. We advance the hypothesis of a hypothalamic source of such amines draining via median eminence into portal vasculature, and name this blood "hypothalamic-hypophysial blood." Besides serving as "classical" neurotransmitters, CAs may also have a direct neurohormonal role in the regulation of the human hypothalamic-hypophysial function.

Fetal calf serum versus human serum: ultrastructural evaluation of protein support influence on human ovarian tissue cryopreservation.

The aim of this study was to examine the effect of the different protein supports in the cryopreservation solution on improving human ovarian tissue preservation after frozen-thawed procedures. Biopsies of ovarian cortical tissue were obtained from 14 subjects. All specimens were cryopreserved using a slow freezing/rapid thawing method in a solution consisting of propanediol and sucrose in different proportions of 3 protein supports: 30% human serum (HS) (solution A), 20% HS (solution B), or 20% fetal calf serum (solution C). After thawing, 191 follicles and a total of 70 samples were analyzed using transmission electron microscopy (TEM). The post-thaw preservation rate of the follicles in solution A was significantly higher with respect to solution C (p < 0.05). Unlike the follicles, the stromal cell morphology was not affected by any of the solutions investigated. By comparing stromal morphology and the patient age, it was found that HS better preserved the tissue in patients over 20 years of age with respect to younger ones, which showed a wider variability in ovarian preservation. TEM evaluation showed that 30% HS is more suitable for human ovarian tissue cryopreservation, and research should be focused on defining cryopreservation protocols specific to young patients.

Different gonadotropin pulsatile fashions in anovulatory cycles of young girls indicate different maturational pathways in adolescence.

To characterize the spectrum of pulsatile gonadotropin secretion during the postmenarchal period, we studied 24 adolescents whose gynecological age was 1-4 yr. Six women with ovulatory cycles formed a control group. Eighteen women with anovulatory cycles were grouped on the basis of mean plasma LH values: group 1 (n = 8) with high LH values and group 2 (n = 10) with normal LH values. In all women, plasma gonadotropin concentrations were measured at 10-min intervals for 8 h on day 4 of the cycle. Pulsatile gonadotropin secretion was also studied a second time in 7 women from group 1 and 7 from group 2 after 5 days of progesterone (P) in oil treatment to assess the role of P in regulating gonadotropin secretion in the postmenarchal period. Group 1 had more frequent and greater LH pulses than the other two groups (which were very similar) and had the highest plasma 17 beta-estradiol, testosterone (T), androstenedione (A), and 17-hydroxyprogesterone concentrations. In all anovulatory women, basal LH values were correlated with the LH interpulse interval (r = -0.65; P less than 0.01) and pulse amplitude (r = 0.86; P less than 0.001). LH pulse amplitude was correlated with basal 17 beta-estradiol values (r = 0.74; P less than 0.001), and LH interpulse interval with basal T (r = -0.83; P less than 0.001), A (r = -0.51; P less than 0.05), and 17-hydroxyprogesterone (r = -0.79; P less than 0.001) values. P administration decreased LH pulse frequency and increased LH pulse amplitude more in group 2 than in group 1 with high LH values; a clear reduction was also found in A, T, and 5 alpha-dihydrotestosterone values. These results indicate that 1) anovulatory young women with high plasma LH values have an alternative maturational pathway, different from that of anovulatory women with normal plasma LH values, who are similar to ovulatory adolescents; 2) the pulsatile pattern of gonadotropin secretion has specific roles linked separately to amplitude and frequency in controlling ovarian steroidogenesis, which accounts for the endocrine differences between groups; and 3) in the postmenarchal period, by modulating LH and FSH pulsatility and thus reducing androgen levels and their atretic action on follicles, P may be a basic regulatory factor in enhancing functional cyclicity.

Adeno-pituitary hormones in human hypothalamic hypophysial blood.

An in vivo technique for collecting blood from the pituitary stalk using transphenoidal microsurgery has recently been developed in men with nonfunctioning pituitary disease. To determine the origin of this blood and the direction of the stream, we measured contemporaneously the levels of LH, FSH, PRL, GH, TSH, and ACTH in hypothalamic-hypophysial blood (HHB) and peripheral blood (PB). Eleven patients with nonfunctioning pituitary adenomas entered the study. The surgical procedure used for collecting HHB consisted of periodically aspirating small amounts of blood using a microsuction apparatus, just after tumor removal, kept in the postero-superior corner of the sella turcica at the junction of the diaphragm with the dursum sellae. The data show clearly the existence of a dramatic concentration gap in HHB vs. PB in all adeno-pituitary hormones (P = 0.003). The HHB/PB ratio varied from 50-600 in the different hormones. The secretion of adeno-pituitary hormones in blood drawn at the pituitary stalk level in man was reported for the first time. The dramatic HHB/PB ratio of the hormone levels has been emphasized. The most likely explanation for the markedly elevated hormone concentration gradient between central and peripheral blood was sampling of peri- and/or suprapituitary blood. To consider the origin and direction of the HHB stream, two hypotheses have been further advanced: 1) a retrograde bloodflow from the pituitary, and 2) a central-hypothalamic secretion.

Longitudinal evaluation of the different gonadotropin pulsatile patterns in anovulatory cycles of young girls.

We studied 13 adolescents (mean gynecological age 29.2 +/- 14.1 months) with anovulatory cycles and 7 women with ovulatory cycles (mean gynecological age 33.1 +/- 15.3 months) as a control group. Adolescents with anovulatory cycles were grouped on the basis of mean plasma LH values: group 1 (n = 7) with high LH values, and group 2 (n = 6) with normal LH values. In all women plasma gonadotropin concentrations were measured at 10-min intervals for 8 h on day 4 of the cycle. Pulsatile gonadotropin secretion was also studied in each subject a second time 40 months later, to establish the outcome of the different pulsatile patterns. Group 1 had more frequent and greater LH pulses than the other two groups (which were similar) and had the highest plasma 17 beta estradiol, testosterone, androstenedione, and 17 hydroxyprogesterone concentrations. Longitudinal control showed that: in group 1, three subjects out of seven acquired ovulatory cycles and there was a fall in mean LH plasma levels (30 +/- 5 vs. 9 +/- 4 IU/L; P less than 0.01), number of pulses (8.3 +/- 1.5 vs. 5 +/- 0; P less than 0.025), mean amplitude (13 +/- 3 vs. 5 +/- 2 IU/L; P less than 0.02) and an increase in interpulse interval (56 +/- 10 vs. 91 +/- 6 min; P less than 0.01). In four subjects anovulatory cycles persisted and the LH pulsatile profile remained unchanged. In group 2, five subjects out of six acquired ovulatory cycles, but there were no significant changes in the number of pulses (6 +/- 1 vs. 6 +/- 2; P = NS), interpulse interval (97 +/- 30 vs. 85 +/- 30 min; P = NS), or amplitude (5 +/- 2 vs. 4 +/- 2 IU/L; P = NS). The results indicate that: 1) anovulatory young women with early normal plasma LH values have an adequate GnRh pulsatile pattern which will easily lead to ovulation; 2) anovulatory young women with high LH plasma values may have a reproductive system blocked in a pathological condition, similar to that observed in polycystic ovary syndrome; 3) only few subjects with high plasma LH values are able to achieve ovulation and normalize LH pulsatile pattern as a consequence of a new mode of GnRh release.