Luteal phase support for assisted reproductive technologies: between past, present and future.

The luteal phase is defined as the period between ovulation and either the establishment of a pregnancy or the onset of menses two weeks later. Assisted reproductive technologies (ART), and in particular controlled ovarian stimulation (COS), negatively interfere with the endocrine mechanisms normally regulating the luteal phase. Up to now, there is no generally accepted opinion as to the most appropriate therapeutic schemes for luteal phase support in ART cycles. Progesterone-based protocols are the most frequently adopted, while alternative regimens including human chorionic gonadotropin (hCG) and GnRH agonists (GnRH-a) are controversial. A GnRH-a can be used instead of hCG for ovulation triggering and the effectiveness of luteal phase support in such new protocols is the object of a growing number of experimental studies. Currently, vaginal progesterone is considered as the first line therapy for luteal phase support (LPS). The starting-time and the duration of luteal phase supplementation after the onset of pregnancy are still debated. Despite the lack of clinical or biological evidence supporting the efficacy of luteal phase support in intrauterine insemination cycles, the use of progesterone has become a well-established practice.

In vitro fertilization stimulation protocol for normal responder patients.

The aim of this prospective observational study is to determine the different outcomes of IVF/ICSI treatments after using antagonists or agonists of gonadotrophin-releasing hormone (GnRH) for controlled ovarian hyperstimulation (COH) in normal responder patients. Two hundred forty-seven patients undergoing IVF treatment at the Centre of Reproductive Medicine, Rome (CERMER), from January 2005 to December 2008, were included in the study. Patients were stimulated either with a standard long protocol with GnRH agonists (n = 156) or with GnRH antagonists (n = 91). The use of GnRH antagonists resulted in a significant reduction in the duration of the stimulation (Agonist Group 14.10 ± 2.25 vs Antagonist Group 11.34 ± 2.11; p < 0.001) and in the amount of gonadotrophin (IU of r-FSH) needed (Agonist Group 1878 ± 1109 vs Antagonist Group 1331 ± 1049; p = 0.0014). Moreover a lower number of cycles were cancelled with the antagonist protocol (4.39 vs 6.41%). The GnRH antagonist protocol, when compared to the GnRH agonist one, is associated with a similar clinical pregnancy rate, similar implantation rate, significantly lower gonadotrophin requirement and shorter duration of stimulation. For this reason, GnRH antagonists might be a good treatment even for normal responder patients undergoing IVF.

Heavy metals and placental fetal-maternal barrier: a mini-review on the major concerns.

BACKGROUND: Heavy metals (HMs) are environmental contaminants with toxic properties for wildlife and humans. The placenta is a privileged organ that, along with the fetal membranes and amniotic fluid, enables growth and development of the fetus during the physiological pregnancy. It also acts as a filter reducing the passage of harmful substances, protecting the embryo and then the fetus from exposure to pollutants. The placental barrier is not completely impermeable to the passage of harmful substances; indeed, HMs were detected not only in placental tissues, but also in amniotic fluid and umbilical cord blood. The amniotic fluid can be considered as a valuable marker of prenatal exposure to exogenous factors, and as an indicator of the integrity of placental barrier. The effect of an intrauterine exposure to heavy metals has been amply evaluated during the last decades. Several studies investigated the exposure to HMs in order to evaluate the mechanism of placental transfer and the impact on fetuses and later children's health. In particular,  the early exposure to Pb, Hg, and Cd was correlated to infant health effects, such as neurological, developmental, and endocrine disorders. The aim of this mini-review is to summarise the current state of knowledge about the interaction between HMs and placental barrier, considering possible implications on fetal health.

GnRH antagonists in assisted reproductive techniques: a review on the Italian experience.

Current Controlled Ovarian Stimulation (COH) for Assisted Reproductive Techniques (ART) pursues three main objectives: hypophyseal activity suppression, multiple follicle growth stimulation, and ovulation induction. By suppressing hypophyseal activity, it is possible to prevent untimely LH surge and allow the appropriate development of the leading follicle. The classical GnRH agonist long protocol is the most widely used in COH for ART. However, an alternative regimen based on GnRH antagonist has been recently introduced in clinical practice. As competitive antagonists, these drugs display an immediate and quickly reversible effect and they avoid hormonal withdrawal side effects. Moreover, this protocol shows undeniable advantages, including the shorter duration of the treatment, the lower amount of gonadotropin required, the shorter hormonal and ultrasound monitoring of patients, milder physical and emotional stress, and a lower risk of Ovarian Hyperstimulation Syndrome (OHSS). The use of GnRH antagonists was traditionally restricted to selected patients, as "poor responders" and women at high-risk of developing OHSS such as Polycystic Ovary Syndrome (PCOS) and patients who had previously experienced OHSS. These findings could prompt a trend to change from the standard agonist protocol to the antagonist protocol in all categories of patients. This review provides a comprehensive overview of the use of GnRH antagonist protocols applied both to IVF techniques and to IUI procedures in the Italian experience.

The addition of GnRH antagonists in intrauterine insemination cycles: a pilot study.

AIM: This prospective study was designed to assess whether the use of GnRH antagonists can improve the success rate of controlled ovarian stimulation (COS) in intrauterine insemination (IUI) treatments. PATIENTS AND METHODS: Eighty patients were divided into two groups: GnRH antagonist group (Group A, n=40) and control group (Group B, n=40). Patients in Group B underwent COS with recombinant Follicle Stimulating Hormone (r-FSH, 50-75 IU/d) only, while patients in Group A were administered r-FSH (50-75 IU/d) plus cetrorelix (0.25 mg/d, starting when ≥ 2 follicles ≥ 14 mm were detected on ultrasound scan). In both groups a single insemination was performed 36 hours after human Chorionic Gonadotropin (hCG, 250 mcg) administration. The primary outcome was clinical Pregnancy Rate (PR). Secondary outcomes were ongoing PR, incidence of Premature Luteinization (PL), number of follicles with mean diameter ≥ 16 mm and between 11 and 15 mm on the day of hCG administration, miscarriage rate, cycle cancellation rate, total amount of r-FSH used and duration of treatment. Student's t test and Chi-square test were used (p < .05 statistically significant). RESULTS: A total of 146 cycles were performed (Group A: n=72; Group B: n=74). A trend towards higher PR in Group A was detected, although it was not statistically significant (Clinical PR: 18.05% vs 10.81%). The number of follicles ≥ 16 mm was significantly increased in Group A. The incidence of both premature LH surge and premature luteinization (PL) was significantly higher in Group B. No significant differences were found in the duration of the stimulation protocol, and in the total amount of r-FSH administered. CONCLUSIONS: The addition of GnRH antagonist in COS/IUI protocol significantly increases the number of mature follicles. However, this multifollicular recruitment is not linked to a significantly higher PR.

[Administration of micronized palmitoylethanolamide (PEA)-transpolydatin in the treatment of chronic pelvic pain in women affected by endometriosis: preliminary results]. / Utilizzo della Palmitoiletanolamide micronizzata (PEA)- transpolidatina nel trattamento del dolore pelvico cronico in donne affette da endometriosi: risultati preliminari.

AIM: Aim of the study was to evaluate the effectiveness of micronized palmitoylethanolamide (PEA)-transpolydatin in the treatment of chronic pelvic pain in women affected by endometriosis. METHODS: Twenty-four patients with suspected endometriosis affected by severe pelvic pain were enrolled. All patients received two tablets a day of PEA 400 mg and 40 mg polydatin for 90 days consecutively. A Visual Analogic Scale was used for the assessment of the severity of global pain, dysmenorrhea, dyspareunia, dysuria and dischezia. A second questionnaire was submitted to patients to assess the quality of life. The compilation of a diary lead us to evaluate the monthly assumption of any painkillers. Patients were evaluated at the begin of the treatment and then monthly until the end of the study (90 days). The statistical analysis was performed by using the ANOVA for the analysis of variance. RESULTS: Statistically significant results were found in relation to pelvic pain, dysmenorrhea and dyspareunia compared to the initial evaluation of patients. Results related to dysuria and dischezia were not statistically significant (P>0.05). The decrease in pelvic pain leads to an improvement of the quality of life of patients. A decreased assumption of nonsteroidal anti-inflammatory drugs (NSAIDs) was also observed. CONCLUSION: PEA could be considered an effective supplement to conventional analgesic therapies in the management of pelvic pain related to endometriosis.

Tertiary hyperparathyroidism: a review.

ABSTRACT: Tertiary hyperparathyroidism (HPT III) occurs when an excess of parathyroid hormone (PTH) is secreted by parathyroid glands, usually after longstanding secondary hyperparathyroidism. Some authorities reserve the term for secondary hyperparathyroidism that persists after successful renal transplantation. Long-standing chronic kidney disease (CKD) is associated with several metabolic disturbances that lead to increased secretion of PTH, including hyperphosphatemia, calcit-riol deficiency, and hypocalcaemia. Hyperphosphatemia has a direct stimulatory effect on the parathyroid gland cell resulting in nodular hyperplasia and increased PTH secretion. Prolonged hypocalcaemia also causes parathyroid chief cell hyperplasia and excess PTH. Af-ter correction of the primary disorder CKD by renal transplant, the hypertrophied parathyroid tissue fails to resolute, enlarge over and continues to oversecrete PTH, despite serum calcium levels that are within the reference range or even elevated. They also may become resistant to calcimimetic treatment. The main indication for treatment is persistent hypercalcemia and/or an increased PTH, and the primary treatment is surgery. Three procedures are commonly performed: total parathyroidectomy with or without autotransplantation, subtotal parathyroidectomy, and limited parathyroidectomy. It is important to remove superior parts of thymus as well. The most appropriate surgical procedure, whether it be total, subtotal, or anything less than subtotal including "limited" or "focused" parathyroidectomies, continues to be unclear and controversial. Surgical complications are rare, and para-thyroidectomy appears to be a safe and feasible treatment option for HPT III.

Ulipristal acetate prior to in vitro fertilization in a female patient affected by uterine fibroids: a case report.

OBJECTIVE: Uterine leiomyomatosis and especially submucosal myomas hamper the outcomes of Assisted Reproductive Techniques (ART). Even though surgical treatment eliminates gross anatomical anomalies, medical treatment should be encouraged to improve the overall structure of the uterus, thereby enabling ART. CASE PRESENTATION: We report the case of an infertile female patient suffering from symptomatic uterine fibromatosis, who received 5 mg/day ulipristal acetate (UPA), a selective progesterone receptor modulator (SPRMs), for three months before and after hysteroscopic myomectomy. Uterine bleeding reduced on the eight days of treatment, with a subsequent improvement of pelvic pain. Under transvaginal ultrasound the uterus appeared globally enlarged with a diffuse leiomyomatosis of the myometrial layer. Saline infusion showed a markedly distorted cavity due two submucosal myomas (sized 31 × 24 mm and 21 × 19 mm, respectively) and one intramural myoma (37 × 34 mm). After three months the size of the myomas was reduced by 30-40%, allowing the hysteroscopic removal of the submucosal fibroids and the bigger intramural one. The smaller fibroids involving the myometrial layer were instead too diffused to be removed. At the conclusion of the subsequent cycle of UPA, the overall appearance of the cavity had improved, and the endometrial layer was regular, allowing the patient to undergo in vitro fertilization (IVF). There was no adverse effect related to treatment, and the endometrial biopsy did not reveal any histologic change. CONCLUSIONS: UPA seems to have a triple effect: it ensures prompt symptom relief, it reduces the size of the myomas enabling surgery and it improves the morphology of the uterus.

Diagnostic findings in adenomyosis: a pictorial review on the major concerns.

Adenomyosis is a benign pathology with a marked impact on women in reproductive age. The prevalence of adenomyosis ranges from 5 to 70%. Dysmenorrhea, metrorrhagia, chronic pelvic pain, dyspareunia and infertility often occur, while a third of the women is asymptomatic. This pictorial review focuses on the peculiar patterns of presentation in adenomyosis. They are identified by means of non-invasive or minimally invasive techniques, with particular reference to 2D- and 3D-transvaginal sonography, sonohysterosalpingography, magnetic resonance imaging, and endoscopic techniques (i.e. hysteroscopy and laparoscopy).

[Administration of MICRONIZED PALMITOYLETHANOLAMIDE (PEA)-transpolydatin in the treatment of chronic pelvic pain in women affected by endometriosis: preliminary results.]

Aim: Aim of the study was to evaluate the effectiveness of micronized palmitoylethanolamide (PEA)-transpolydatin in the treatment of chronic pelvic pain in women affected by endometriosis. Methods: Twenty-four patients with suspected endometriosis affected by severe pelvic pain were enrolled. All patients received two tablets a day of PEA 400 mg and 40 mg polydatin for 90 days consecutively. A Visual Analogic Scale was used for the assessment of the severity of global pain, dysmenorrhea, dyspareunia, dysuria and dischezia. A second questionnaire was submitted to patients to assess the quality of life. The compilation of a diary lead us to evaluate the monthly assumption of any painkillers. Patients were evaluated at the begin of the treatment and then monthly until the end of the study (90 days). The statistical analysis was performed by using the ANOVA for the analysis of variance. Results: Statistically significant results were found in relation to pelvic pain, dysmenorrhea and dyspareunia compared to the initial evaluation of patients. Results related to dysuria and dischezia were not statistically significant (P>0.05). The decrease in pelvic pain leads to an improvement of the quality of life of patients. A decreased assumption of nonsteroidal anti-inflammatory drugs (NSAIDs) was also observed. Conclusion: PEA could be considered an effective supplement to conventional analgesic therapies in the management of pelvic pain related to endometriosis.

Tubal endometrioma within a twisted fallopian tube: a clinically complex diagnosis.

BACKGROUND: Endometriotic lesions affect the fallopian tubes in 6% of patients with endometriosis and adhesions involve the salpinges in 26%. Different studies report that 45%-70% of adolescents with chronic pelvic pain have endometriosis diagnosed at the time of laparoscopy. CASE: We report a case of an 18-year-old girl with a tubal torsion due to a tubal endometrioma. The endometriotic nodule before laparoscopy appeared to be located in the rectovaginal septum. At laparoscopy, a right fallopian tube torsion was visible and several adhesions were connecting the lesion to the pouch of Douglas' walls. SUMMARY AND CONCLUSION: The tenacious adhesions, which welded the nodule to the walls of the pouch of Douglas, did not allow to distinguish at the MRI a tubal endometrioma from a rectovaginal endometriotic mass, justifying the false diagnosis.