Unopposed estrogens: current and future perspectives.

Estrogens and progestogens act on female reproductive tissues in opposite ways. As they counteract each other actions, the correct balance between these two classes of hormones is pivotal to avoid dangerous states. Unopposed estrogens occur when progestogen levels do not balance estrogens, primarily deriving from overproduction of estrogens via aromatase enzyme. In the endometrium, unopposed estrogens induce proliferative or invasive phenomena, which represent the first step toward different diseases. These pathologies include endometrial hyperplasia, endometrial polyps, endometriosis and adenomyosis. Endometrial hyperplasia and polyps are proliferative pathologies, while endometriosis and adenomyosis are characterized by the invasion of other tissues by endometrial cells. Current pharmacological treatments include Gonadotropin-Releasing-Hormone analogs, aromatase inhibitors and progestogens, either alone or in combination with estrogens. As these drugs usually lead to burdensome undesired effects, researchers seek to find new therapeutical molecules. Recent literature highlights the positive effects of metformin, an insulin sensitizing drug that reduces the insulin proliferative stimulus on the endometrium. d-chiro-inositol is an insulin second messenger with insulin sensitizing and mimetic properties, recently described as an aromatase down-regulator. Based on current evidence, d-chiro-inositol may be useful to treat the pathologies responsive to unopposed estrogens.

Assisted reproduction and Coronavirus in Italy.

OBJECTIVE: A novel type of Coronavirus was identified in China in December 2019. The first cases of a form of pneumonia of unknown etiology were detected at the beginning of that month in Wuhan. The virus is believed to have emerged at the Wuhan Huanan Seafood Market, where transmission of a zoonotic pathogen to humans occurred. PATIENTS AND METHODS: Some studies conducted in China during the epidemic report small numbers of pregnant women infected with SARS-CoV-2 and some pregnancy complications in patients with COVID-19. However, they fail to document the transplacental passage of the virus from mother to fetus. RESULTS: Following the COVID-19 outbreak, guidelines for couples who are undergoing treatments of assisted reproduction have been issued by the International Federation for Fertility Societies (IFFS), the American Society for Reproductive Medicine (ASRM), the European Society of Human Reproduction and Embryology (ESHRE) and the Latin American Network of Assisted Reproduction (REDLARA). They recommend couples to discuss assisted reproduction with their doctors while those at risk or with SARS-CoV-2 should consider freezing oocytes or embryos and retransferring them later. CONCLUSIONS: Other than the US, Italy is the country with the highest number of cases (197675 positives, 26644 deaths) (updated on April 26). The Italian National Transplant Centre and the Higher Institute of Health advised on March 17 to complete the cycles already started and not to start new cycles. Phase 2 will begin on 4 May with an increase in freedom of action and fertilization treatments will start again. The Society that brings together embryologists (SIERR) has issued the guidelines to be followed when this happens.

Myo-inositol impact on sperm motility in vagina and evaluation of its effects on foetal development.

OBJECTIVE: To counteract the arising problem of couple infertility, having good quality gametes is increasingly important. A molecule that seems to be useful to favor this condition is myo-inositol (MI), the most common stereoisomer of the inositol family, involved as second messenger in several cell pathways (osmoregulation, chromatin remodeling, gene expression, etc.). To evaluate this possibility, a treatment with myo-inositol in idiopathic infertile couples was performed in this randomized, placebo-controlled study. PATIENTS AND METHODS: 86 couples were enrolled and randomly assigned to two groups, treated either with MI (Xyminal®, Lo.Li. Pharma Srl, Rome, Italy) or placebo suppositories, to evaluate the effects on sperm motility, cervical mucus quality and pregnancy rate. Moreover, in pregnancy cases, all routine controls on gestation progress and foetal health were performed to confirm the safety of this treatment. RESULTS: As showed in this study, MI treatment allows an increase of total sperm motility (54.42 ± 8.72) in comparison to placebo group (46.21 ± 5.33). Moreover, MI mildly improves cervical mucus quality and increases the number of pregnancies (18.60%) in comparison to the placebo group (6.97%). CONCLUSIONS: MI improves sperm motility and cervical mucus quality, increasing the probability of conception. The absence of adverse events both for the mother and the foetus confirmed the safety of this molecule in pregnancy, supporting even more its use for couples seeking pregnancy.

Efficacy of the synergic action of myoinositol, tyrosine, selenium and chromium in women with PCOS.

OBJECTIVE: The aim of the study is to investigate the efficacy of a treatment with myoinositol plus L-tyrosine, selenium, and chromium in women with polycystic ovarian syndrome (PCOS). PATIENTS AND METHODS: One hundred and eighty-six women, with diagnosis of PCOS, were divided in four groups according to their clinical features. Phenotype A: androgen excess + ovulatory dysfunction + polycystic ovarian morphology. Phenotype B: androgen excess + ovulatory dysfunction. Phenotype C: androgen excess + polycystic ovarian morphology. Phenotype D: ovulatory dysfunction + polycystic ovarian morphology. All patients were given daily for six months a compound with 2 g myo-inositol, 0.5 mg L-Tyrosine, 0.2 mg folic acid, 55 mcg selenium, 40 mcg chromium. Hormonal assessment, BMI, Ferriman-Gallway Gallway score, HOMA index, and follicular monitoring were reported before starting the therapy, three months and six months after. RESULTS: Phenotype A showed an improvement, consistent with restored ovulation: more regular length of the menstrual cycle, detection of periovulatory follicle at ultrasound, and rising of progesterone in the luteal phase. A total of 45 patients (65.2%) ovulated after six months. In the same period glucose and HOMA index decreased. In the phenotype B, 80% of patients ovulated after six months. An improvement of the clinical and biochemical sign of hyperandrogenism was also reported. In the phenotype C, after BMI had followed the treatment for six months, it decreased in a statistically significant manner. In the phenotype D, 49 out of 82 women (59.7%) restored their regular menstrual period and ovulated. CONCLUSIONS: Our study reported how the synergistic action of myoinositol, L-tyrosine, selenium, and chromium could restore normal menstrual cycle, ovulation, and decrease weight in these patients.

[Use of the TUT (Tension-free Vaginal Tape) in the treatment of female urinary stress incontinence. Preliminary results]. / Utilizzazione del TVT (Tension-free Vaginal Tape) nel trattamento dell'incontinenza urinaria femminile da sforzo. Risultati preliminari.

BACKGROUND: The Tension-free Vaginal Tape (TVT) represents the most recent technique for the treatment of genuine stress urinary incontinence (GSUI). The various number of surgical procedures proposed for the treatment of GSI very often do not lead to a complete remission of this pathology. The data from the literature show how TVT is a effective procedure for the treatment of female urinary incontinence. METHODS: Twenty-nine women with diagnosis of urinary incontinence underwent application of polypropilene band (TVT: tension-free vaginal tape) underneath the uretra, in order to treat this disorder. The procedure has been carried out in peripheral anesthesia. RESULTS: A complete remission of the urinary incontinence was obtained in 24 patients. In the remaining cases there was an improvement of the symptoms in two patients, whereas in two patients remained a secondary detrusor instability. In one case the external iliac vein was perforated thus requiring a surgical repair. CONCLUSION: The short surgical time, the feasibility of the procedure and the following short hospitalization made this technique well accepted either by the surgeons ang the patients. Moreover the possibility to carry out the procedure in peripheral anesthesia allows to have the collaboration of the patient. However this technique is not free of risks, how the serious complication we had can demonstrate.

Ovarian blood flow before and after conservative laparoscopic treatment for endometrioma.

To evaluate the vascular changes in ovaries affected by endometriomas 28 women with ovarian endometriosis underwent transvaginal ultrasound with color flow imaging and blood flow analysis of the ovarian artery before and after laparoscopic conservative treatment of the ovarian cyst. Mean pulsatility index (P.I.) and resistance index (R.I.) of the ovarian artery on the side affected by endometrioma were compared using Student's t-test. Mean P.I. after laparoscopy (1.59) was significantly lower (p = 0.001) than before surgical intervention (2.17). Analogously the mean R.I. was significantly different (p = 0.001) when compared before (0.81) and after (0.73) laparoscopy. Color Doppler velocimetry may add greater understanding of the ovarian hemodynamic changes that occur after conservative surgery on the ovary.

Unusual case of caudal duplication (dipygus).

We report the case of a dipygus diagnosed by sonography in the second trimester that had 6 lower extremities, double external male genitalia, a megabladder, 3 dilated ureters, and a polycystic right and a pelvic left kidney. This complex malformation represents a rare type of caudal duplication.

[Primary microinvasive adenocarcinoma of the cervix. A clinical case]. / Adenocarcinoma primitivo microinvasivo dell'esocervice. Caso clinico.

In this case the authors describe a patient with primary microinvasive adenocarcinoma of the eso-cervix, with the cervical canal not involved by the pathology, diagnosed by colposcopy followed by biopsy. Before the diagnosis of microinvasive adenocarcinoma the patient was scheduled for electrocautery of the suspicious area due to the fact that previous Pap-smears had always been negative. The authors underline the important role of colposcopy as a diagnostic tool that should be mandatory before any surgical therapy on the cervix and that allowed to diagnose such a rare cervical tumor.

Laparoscopic Lymphadenectomy and Vaginal Radical Hysterectomy for the Treatment of Cervical Cancer

The choice of treatment (surgery, radiotherapy) for cervical carcinoma depends on surgical staging. The noninvasive approach for node evaluation is not very accurate; therefore lymph node metastasis has to be determined surgically. Seventeen women with cervical cancer underwent bilateral laparoscopic lymphadenectomy with dissection of the common iliac, hypogastric, and external iliac vessels and the obturator nerve. The average number of lymph nodes sampled was 14 (range 12-24 nodes). The mean duration of lymphadenectomy was 60 minutes (range 50-90 min). Based on preoperative evaluation and on the pathology report, a radical vaginal hysterectomy (Schauta-Amreich) was performed in all women at the end of laparoscopy. All laparoscopies and radical hysterectomies were uneventful. Based on this preliminary experience, laparoscopic lymphadenectomy may play an important role in reviving radical vaginal hysterectomy in women with cervical cancer. Followed by vaginal radical hysterectomy, it may be the treatment of choice in early disease, avoiding an abdominal incision.

Use of medroxyprogesterone acetate in the prevention of postoperative adhesions.

OBJECTIVES: To evaluate the efficacy of a commonly used progestogen, medroxyprogesterone acetate (MPA), in the prevention of postoperative adhesion formation. DESIGN: A double-blind, controlled study evaluated the efficacy of MPA to reduce postoperative adhesion formation and compared it with other adjuvants and controls in a rat model. SETTING: Animal Care Facility of an academic research setting. SUBJECTS: Seventy-five Sprague-Dawley female rats randomly divided into five groups. INTERVENTIONS: Three weeks before surgery, the animals from each group were administered an IM injection of one of the following regimens: [1] 15 mg MPA; [2] both 15 mg MPA and 0.75 mg leuprolide acetate (LA); [3] 0.75 LA; or [4] and [5] comparable volumes of sterile saline. A standardized surgical trauma was inflicted in all animals. Before abdominal closure, 2 mL of Ringer's Lactate was instilled in the abdominal cavity of all groups except group 5 (controls). Three weeks after surgery, the rats were killed and the adhesions were scored on a scale of 0 to 3 according to their size, thickness, and vascularity. MAIN OUTCOME MEASURE: Postoperative adhesions. RESULTS: The preoperative administration of MPA resulted in the least number and the least severe adhesions. The combination of LA and MPA did not reduce postoperative adhesion formation. Both Ringer's Lactate and LA reduced postoperative adhesions but not to the same extent as MPA. CONCLUSION: The preoperative administration of MPA in our laboratory animal model results in the most significant reduction of postoperative adhesion formation. This action of MPA may be mediated by the induction of both a progestational and a hypoestrogenemic milieu. However, the ultimate role of MPA in a clinical situation requires further investigation.

Laparoscopic treatment of ovarian endometrioma. One year follow-up.

Thirty-six women with ultrasonographic diagnosis of ovarian endometrioma (bilateral in nine of them), have been treated laparoscopically. After the surgical procedure the patients were assigned to one of the following regimes: Gn-RH-a for 3 months, oral contraceptives if they wanted to avoid pregnancy, or nothing. The follow-up consisted in 1-3-6-12 months ultrasound. The first recurrences were observed at the 6-month ultrasound with an overall recurrence rate after 12 months of 11%. Improvement of pain symptoms occurred in 87% of the patients and fertility rate was 45%.

Menstrual patterns, pain symptoms, body mass index and smoking habits in women with endometriosis.

Epidemiologic studies have investigated the risk factors for endometriosis, but currently the results are still controversial. The aim of this study is to evaluate the incidence of some of the risk factors that have been involved with endometriosis to better understand the natural history and evolution of this disease. The medical records of 186 women with laparoscopic diagnosis of endometriosis were studied. We analysed the characteristics of the menstrual cycle, the presence of pain symptoms and the familiarity for endometriosis. Moreover, the body mass index of all patients and the average cigarettes smoked per day were calculated. Despite the fact that some of the data collected resulted to be statistically significant when compared among the four stages of endometriosis, the roles of the many factors that have been associated with the risk or the evolution of pelvic endometriosis still remain unknown.

[Premature ovarian failure: etiopathogenic evaluation and therapeutic possibilities]. / Deficit ovarico prematuro (POF): inquadramento nosologico e possibilità di terapia.

Premature ovarian failure (POF) is a syndrome due to many etiologies, whose underlying mechanisms aren't completely understood yet. Consequently there are important therapeutic implications. The authors describe their experience treating patients with POF using hormonal replace therapy and ovulation induction therapy in order to restore or replace the early loss of reproductive capacity.

[A rare case of ectopic pregnancy. Primary ovarian pregnancy]. / Raro caso di gravidanza ectopica. Gravidanza ovarica primitiva.

A rare case of primary ovarian pregnancy is reported. The multiple diagnostic problems and the unclear symptomatology delayed the time of the definitive diagnosis more than seventy five days. All the histological criteria for the classification of an ovarian pregnancy are faced in this case. The finding of a well conserved gestational sac and embryo inside the ovarian tissue makes this case even more rare and interesting. When there is a suspicion of ectopic or ovarian pregnancy the Authors strongly suggest an early laparoscopy to make a reliable and precocious diagnosis, avoid the risk of the hemoperitoneum, perform a conservative therapy and preserve the ovarian function with the patient's reproductive potential.