Heavy Metals in Follicular Fluid Affect the Ultrastructure of the Human Mature Cumulus-Oocyte Complex.

It is known that exposure to heavy metal such as lead (Pb) and cadmium (Cd) has several adverse effects, particularly on the human reproductive system. Pb and Cd have been associated with infertility in both men and women. In pregnant women, they have been associated with spontaneous abortion, preterm birth, and impairment of the development of the fetus. Since these heavy metals come from both natural and anthropogenic activities and their harmful effects have been observed even at low levels of exposure, exposure to them remains a public health issue, especially for the reproductive system. Given this, the present study aimed to investigate the potential reproductive effects of Pb and Cd levels in the follicular fluid (FF) of infertile women and non-smokers exposed to heavy metals for professional reasons or as a result of living in rural areas near landfills and waste disposal areas in order to correlate the intrafollicular presence of these metals with possible alterations in the ultrastructure of human cumulus-oocyte complexes (COCs), which are probably responsible for infertility. Blood and FF metals were measured using atomic absorption spectrometry. COCs corresponding to each FF analyzed were subjected to ultrastructural analyses using transmission electron microscopy. We demonstrated for the first time that intrafollicular levels of Pb (0.66 µg/dL-0.85 µg/dL) and Cd (0.26 µg/L-0.41 µg/L) could be associated with morphological alterations of both the oocyte and cumulus cells' (CCs) ultrastructure. Since blood Cd levels (0.54 µg/L-1.87 µg/L) were above the current reference values established by the guidelines of the Agency for Toxic Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA) (0.4 µg/L), whereas blood Pb levels (1.28 µg/dL-3.98 µg/dL) were below the ATSDR reference values (≤5 µg/dL), we believe that these alterations could be due especially to Cd, even if we cannot exclude a possible additional effect of Pb. Our results highlighted that oocytes were affected in maturation and quality, whereas CCs showed scarcely active steroidogenic elements. Regressing CCs, with cytoplasmic alterations, were also numerous. According to Cd's endocrine-disrupting activity, the poor steroidogenic activity of CCs might correlate with delayed oocyte cytoplasmic maturation. So, we conclude that levels of heavy metals in the blood and the FF might negatively affect fertilization, embryo development, and pregnancy, compromising oocyte competence in fertilization both directly and indirectly, impairing CC steroidogenic activity, and inducing CC apoptosis.

Oocyte competence is independent of the ovulation trigger adopted: a large observational study in a setting that entails vitrified-warmed single euploid blastocyst transfer.

PURPOSE: To assess whether the GnRH-agonist or urinary-hCG ovulation triggers affect oocyte competence in a setting entailing vitrified-warmed euploid blastocyst transfer. METHODS: Observational study (April 2013-July 2018) including 2104 patients (1015 and 1089 in the GnRH-a and u-hCG group, respectively) collecting ≥1 cumulus-oocyte-complex (COC) and undergoing ICSI with ejaculated sperm, blastocyst culture, trophectoderm biopsy, comprehensive-chromosome-testing, and vitrified-warmed transfers at a private clinic. The primary outcome measure was the euploid-blastocyst-rate per inseminated oocytes. The secondary outcome measure was the maturation-rate per COCs. Also, the live-birth-rate (LBR) per transfer and the cumulative-live-birth-delivery-rate (CLBdR) among completed cycles were investigated. All data were adjusted for confounders. RESULTS: The generalized-linear-model adjusted for maternal age highlighted no difference in the mean euploid-blastocyst-rate per inseminated oocytes in either group. The LBR per transfer was similar: 44% (n=403/915) and 46% (n=280/608) in GnRH-a and hCG, respectively. On the other hand, a difference was reported regarding the CLBdR per oocyte retrieval among completed cycles, with 42% (n=374/898) and 25% (n=258/1034) in the GnRh-a and u-hCG groups, respectively. Nevertheless, this variance was due to a lower maternal age and higher number of inseminated oocytes in the GnRH-a group, and not imputable to the ovulation trigger itself (multivariate-OR=1.3, 95%CI: 0.9-1.6, adjusted p-value=0.1). CONCLUSION: GnRH-a trigger is a valid alternative to u-hCG in freeze-all cycles, not only for patients at high risk for OHSS. Such strategy might increase the safety and flexibility of controlled-ovarian-stimulation with no impact on oocyte competence and IVF efficacy.

Natural Cycle Results in Lower Implantation Failure than Ovarian Stimulation in Advanced-Age Poor Responders Undergoing IVF: Fertility Outcomes from 585 Patients.

To compare pregnancy rate and implantation rate in poor responder women, aged over 40 years, who underwent natural cycle versus conventional ovarian stimulation. This is a retrospective single-center cohort study conducted at the GENERA IVF program, Rome, Italy, between September 2012 and December 2018, including only poor responder patients, according to Bologna criteria, of advanced age, who underwent IVF treatment through Natural Cycle or conventional ovarian stimulation. Between September 2012 and December 2018, 585 patients were included within the study. Two hundred thirty patients underwent natural cycle and 355 underwent conventional ovarian stimulation. In natural cycle group, both pregnancy rate per cycle (6.25 vs 12.89%, respectively, p = 0.0001) and pregnancy rate per patient101 with at least one embryo-transfer (18.85 vs 28.11% respectively, p = 0.025) resulted significant reduced. Pregnancy rate per patient managed with conventional ovarian stimulation resulted not significantly different compared with natural cycle (19.72 vs 15.65% respectively, p = 0.228), but embryo implantation rate was significantly higher in patients who underwent natural cycle rather than patient subjected to conventional ovarian stimulation (13 vs 8.28% respectively, p = 0.0468). No significant difference could be detected among the two groups in terms of abortion rate (p = 0.2915) or live birth pregnancy (p = 0.2281). Natural cycle seems to be a valid treatment in patients over 40 years and with a low ovarian reserve, as an alternative to conventional ovarian stimulation.

Luteal phase after conventional stimulation in the same ovarian cycle might improve the management of poor responder patients fulfilling the Bologna criteria: a case series.

OBJECTIVE: To assess the clinical contribution of luteal-phase stimulation (LPS) to follicular-phase stimulation (FPS) in a single ovarian cycle (DuoStim) for poor responder patients fulfilling the Bologna criteria. DESIGN: Observational study (years 2015-2017) including women satisfying ≥2 of the following characteristics: maternal age ≥40 years and/or ≤3 oocytes retrieved after previous conventional stimulation and/or reduced ovarian reserve (i.e., antral follicle count <7 follicles or antimüllerian hormone <1.1 ng/mL). The LPS was started regardless of the outcome of the FPS. SETTING: Private in vitro fertilization center. PATIENT(S): A total of 100 of 297 patients fulfilling the Bologna criteria chose to undergo DuoStim. INTERVENTION(S): The FPS and LPS with the same antagonist protocol and agonist trigger, intracytoplasmic sperm injection with ejaculated sperm, preimplantation genetic testing for aneuploidies, and vitrified-warmed euploid single blastocyst transfer. MAIN OUTCOME MEASURE(S): The contribution of LPS to the cumulative live birth rate (CLBR) per intention-to-treat (ITT). RESULT(S): Patients (100) underwent FPS (maternal age, 42.1 ± 1.4 y; previous in vitro fertilization cycles with ≤3 collected oocytes, 0.7 ± 0.9; antral follicle count, 3.8 ± 1.2 follicles; and antimüllerian hormone, 0.56 ± 0.3 ng/mL). Ninety-one patients completed DuoStim. All patients were included in the analysis. More oocytes were obtained after LPS with similar developmental and chromosomal competence as paired FPS-derived ones. The CLBR per ITT increased from 7% after FPS to 15% after DuoStim. Conversely, the CLBR per ITT among the 197 patients that chose a conventional controlled ovarian stimulation strategy was 8%, as only 17 patients who were not pregnant returned for a second stimulation after the first attempt (drop-out rate, 81%). CONCLUSION(S): The LPS-derived oocytes increased the CLBR per ITT in a single ovarian cycle in patients fulfilling the Bologna criteria. The DuoStim strategy is promising to manage this thorny population of patients, especially to avoid discontinuation after a first failed attempt.

Radiations and female fertility.

Hundreds of thousands of young women are diagnosed with cancer each year, and due to recent advances in screening programs, diagnostic methods and treatment options, survival rates have significantly improved. Radiation therapy plays an important role in cancer treatment and in some cases it constitutes the first therapy proposed to the patient. However, ionizing radiations have a gonadotoxic action with long-term effects that include ovarian insufficiency, pubertal arrest and subsequent infertility. Cranial irradiation may lead to disruption of the hypothalamic-pituitary-gonadal axis, with consequent dysregulation of the normal hormonal secretion. The uterus might be damaged by radiotherapy, as well. In fact, exposure to radiation during childhood leads to altered uterine vascularization, decreased uterine volume and elasticity, myometrial fibrosis and necrosis, endometrial atrophy and insufficiency. As radiations have a relevant impact on reproductive potential, fertility preservation procedures should be carried out before and/or during anticancer treatments. Fertility preservation strategies have been employed for some years now and have recently been diversified thanks to advances in reproductive biology. Aim of this paper is to give an overview of the various effects of radiotherapy on female reproductive function and to describe the current fertility preservation options.

Complication and recurrence rate in laser CO2 versus traditional surgery in the treatment of Bartholin's gland cyst.

PURPOSE: The treatment of Bartholin's gland cysts by traditional surgery is characterized by some disadvantages and complications such as hemorrhage, postoperative dyspareunia, infections, necessity for a general anesthesia. Contrarily, CO2 laser surgery might be less invasive and more effective as it solves many problems of traditional surgery. The aim of our study is to describe CO2 laser technique evaluating its feasibility, complication rate and results vs traditional surgery. METHODS: Among patients treated for Bartholin's gland cyst, we enrolled 62 patients comparing traditional surgical excision vs CO2 laser surgery of whom 27 patients underwent traditional surgery, whereas 35 patients underwent CO2 laser surgery. Mean operative time, complication rate, recurrence rate and short- and long-term outcomes were assessed. RESULTS: The procedures required a mean operative time of 9 ± 5.3 min for CO2 laser surgery and 42.2 ± 13.8 for traditional surgery. Two patients (5.7 %) needed an hemostatic suture for intraoperative bleeding in the laser CO2 laser technique against 14.8 % for traditional surgery. Carbon dioxide allows a complete healing in a mean time of 22 days without scarring, hematomas or wound infections and a return to daily living in a mean time of 2 days. Instead, patients undergone traditional surgery required a mean time of 14 days to return to daily life with a healing mean time completed in 28 days. CONCLUSIONS: The minimum rate of intra- and post-operative complications, the ability to perform it under local anesthesia in an outpatient setting make CO2 laser surgery more cost-effective than traditional surgery.

Clinical factors and malignancy in endometrial polyps. Analysis of 1027 cases.

STUDY OBJECTIVE: To assess the prevalence of polyps carrying a malignancy and match association between clinical factors and oncologic progression. STUDY DESIGN: A retrospective study (Canadian Task Force classification II-3) at a university hospital in Rome, Italy. We retrospectively analyzed data from 1027 women consecutively treated for endometrial polyps at our center in the period 2002-2011. The association of malignancy with hormonal status, tamoxifen, hypertension, symptoms, diabetes mellitus, obesity, and hormonal replacement therapy in pre- and post-menopausal women was assessed. RESULTS: Mean age was 45.8±10.8 years. Benign polyps accounted for 95.8% of the total, pre-malignant for 2.67%, malignant for 1.54%. Our data showed that post-menopausal and older women (>60y) with endometrial polyps have a higher risk of developing a related endometrial cancer (OR: 3.05, 95% CI [1.54, 6.19], p<0.001 and OR: 2.8, 95% CI [1.38, 5.56], p≤0.003. Also we observed that women with AUB in the post-menopausal period displayed a risk of malignancy (OR: 31.1, 95% CI [10.3,111], p value <0.001). CONCLUSION: Special attention should be drawn to symptomatic post-menopausal patients that appear to be at higher risk of malignancy. Symptomatic pre-menopausal women and asymptomatic post-menopausal women with polyps may be a group with intermediate-risk. These patients should undergo an individualized management plan, balancing both risks and benefits of surgical intervention after discussion with the patient.

Pregnancy outcome after loop electrosurgical excision procedure for cervical intraepithelial neoplasia.

OBJECTIVE: To determine pregnancy outcomes among women who underwent loop electrosurgical excision procedure (LEEP). METHODS: In a case-control study in Italy, 475 pregnant women who underwent LEEP and 441 untreated pregnant women were enrolled between January 2003 and January 2007. Outcome measures were spontaneous abortion, preterm delivery, and at-term delivery rates. Continuous and discrete variables were analyzed via t, χ(2), and Fisher exact tests. Groups were compared by analysis of variance and Tukey HSD test. RESULTS: The spontaneous abortion rate was 14.5% and 14.1% in the LEEP and untreated groups, respectively. The preterm delivery rate was 6.4% and 5.0% in the LEEP and untreated groups, respectively. The number of women with a cervical length of less than 30mm was higher in the LEEP group, but this did not influence preterm delivery rate (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.53-1.95). Among women with a cervical length of less than 15mm, those treated with a wider removal of cervical tissue showed increased risk of preterm delivery (OR, 5.31; 95% CI, 1.01-28.07). CONCLUSION: The preterm delivery rate was not higher among women who underwent LEEP than among untreated women. Preterm delivery was associated with cone size and cervical length in the second trimester.

Laparoscopic injury of the obturator nerve during fertility-sparing procedure for cervical cancer.

BACKGROUND: Intraoperative injury of the obturator nerve has rarely been reported in patients with gynecological malignancies undergoing extensive radical surgeries. Irreversible damage of this nerve causes thigh paresthesia and claudication. Intraoperative repair may be done by end-to-end anastomosis or grafting when achieving tension-free anastomosis is not possible. CASE PRESENTATION: A 28-year-old woman with stage IB cervical cancer underwent fertility-sparing surgery, including conization and bilateral pelvic lymphadenectomy. The left obturator nerve was damaged intraoperatively during pelvic dissection. CONCLUSION: Immediate laparoscopic repair was successful and there was no functional deficit in the left thigh for six months postoperatively.

Life-threatening bleeding after pelvic lymphadenectomy for cervical cancer: endovascular management of ruptured false aneurysm of the external iliac artery.

Late rupture of external iliac artery pseudo-aneurysm is an uncommon complication in patients who undergo extensive gynecologic radical surgeries. A 28-year-old woman with stage IB cervical cancer underwent pelvic lymphadenectomy and extrafascial trachelectomy. Two months after surgery, massive bleeding from ruptured pseudo-aneurysm of the external iliac artery occurred. Endovascular management with covered stent placement was feasible and safe to stop bleeding.

A case of high-grade leiomyosarcoma of the bladder with delayed onset and very poor prognosis.

Mesenchymal tumors represent a small number of bladder cancer cases. Leiomyosarcoma is the most common histology with over 100 cases reported in the whole literature. This tumor is been historically considered as highly aggressive and showing a poor prognosis. Despite very low survival rates showed in older reports, some authors indicate that some patients could have a better outcome. We report a review of the literature and a case of high-grade LMS of the bladder in a 68 years old woman. Diagnosis was delayed and disease was locally advanced. Symptoms and imaging of our case first oriented to a gynecologic condition with an adnexal or uterine origin of the mass, and, a genitourinary origin could be unveiled only intra-operatively.

Natural-cycle in vitro fertilization in poor responder patients: a survey of 500 consecutive cycles.

OBJECTIVE: To determine the role of the natural cycle for in vitro fertilization (IVF) in poor responder patients. DESIGN: Retrospective survey. SETTING: Private center for assisted reproduction. PATIENT(S): 294 women who were poor responders in a previous IVF cycle. INTERVENTION(S): Analysis of 500 consecutive natural cycles IVF. MAIN OUTCOME MEASURE(S): Number of cycles with oocytes, pregnancy rate per cycle, per transfer, and implantation rate. RESULT(S): Oocytes were found in 391 cases (78.1%), and cleaving embryos suitable for transfer were obtained in 285 cycles (57.0%). Pregnancy was observed in 49 cases, with a pregnancy rate of 9.8% per cycle, 17.1% per transfer, and 16.7% per patient. The patients were subdivided arbitrarily by the women's age into three groups. Patients 35 years old or younger showed a pregnancy rate of 18.1% per cycle, 29.2% per transfer, and 31.7% per patient. Women aged between 36 and 39 years showed a pregnancy rate of 11.7% per cycle, 20.6% per transfer, and 20.3% per patient. Women 40 years old or older showed a pregnancy rate of 5.8% per cycle, 10.5% per transfer, and 9.7% per patient. No differences were found for any of the evaluated parameters, independent of which cycle was the first, the second, third, fourth, or fifth, or further consecutive cycle. CONCLUSION(S): In poor responder patients, natural-cycle IVF is an effective treatment, especially in younger women.

Cetrorelix protocol versus gonadotropin-releasing hormone analog suppression long protocol for superovulation in intracytoplasmic sperm injection patients older than 40.

OBJECTIVE: To determine which protocols work better between cetrorelix and long protocols in older patients in a randomized controlled study. DESIGN: A controlled randomized study in a single private IVF center. SETTING: Infertile women referred to a private IVF center. PATIENT(S): Five hundred sixty-four women 40 years or older undergoing IVF. INTERVENTION(S): At their first IVF cycle, the women were randomized into two study groups using a computer-generated number sequence: 281 cases were treated with the cetrorelix protocol, and 283 patients were treated with a long protocol for controlled ovarian hyperstimulation. MAIN OUTCOME MEASURE(S): Days of stimulation, E(2) on the day of hCG administration, amount of FSH administered, number of oocytes yielded, number of embryos obtained, pregnancy rate, and implantation rate. RESULT(S): Patients treated with the long protocol showed a significantly higher number of oocytes retrieved and a higher pregnancy rate for both the cycle and transfer with respect to the cetrorelix protocol patients. The other parameter evaluated did not show any statistically significant differences. CONCLUSION(S): Our study showed that the long protocol performed better in older women than the cetrorelix protocol and that the GnRH antagonist may be detrimental in older women.

IVF pregnancies: neonatal outcomes after the new Italian law on assisted reproduction technology (law 40/2004).

OBJECTIVE: To compare maternal and neonatal outcome of pregnancies achieved by assisted reproduction technique (ART) according to the guidelines of the newly established Italian ART law 40/2004, with that of naturally conceived. DESIGN: Three hundred and sixty-four ART pregnancies and 304 naturally conceived pregnancies were analyzed in terms of the incidence of obstetric complications and perinatal outcome. Control group was enrolled prospectively after being matched for an extensive number of maternal characteristics. RESULTS: Among singletons, ART pregnancies when compared to naturally conceived pregnancies showed a higher incidence of pregnancy loss (23.4% versus 10.5%) and a lower mean birth weight. A higher but not significant incidence of small for gestational age fetuses was observed in ART pregnancies, compared to those from normally conceived pregnancies (7.2% versus 2.7%). Moreover, the ART pregnancies showed a slightly, but nonetheless significantly shorter mean gestational age (38.6 versus 39.3 weeks) and more frequent preterm deliveries (11%) than the control group (2.7%). No difference was found in terms of other obstetric complications such as pregnancy-induced hypertension, gestational diabetes and placental abruption. Neonatal outcome was similar in both groups. CONCLUSION: Although the obstetric outcome among singleton ART pregnancies was good, these patients should be considered obstetric risk cases. The different frequency of complications is not related to maternal age or parity and could be the consequence of infertility or the procedures by which these women conceived. The reasons are, however, unclear and further studies are necessary.

Use of a medium buffered with N-hydroxyethylpiperazine-N-ethanesulfonate (HEPES) in intracytoplasmic sperm injection procedures is detrimental to the outcome of in vitro fertilization.

OBJECTIVE: This study was conducted to determine whether N-hydroxyethylpiperazine-N-ethanesulfonate (HEPES)-buffered medium used for the microinjection of sperm into oocytes may be detrimental for the embryo. DESIGN: Controlled randomized study. SETTING: Private IVF center. PATIENT(S): Women (n = 708) undergoing ICSI. INTERVENTION(S): The women were randomized into two study groups: 2,204 oocytes from 357 women were treated using a medium buffered with bicarbonate without HEPES during the ICSI procedure, and 2,168 oocytes from 351 women were treated using a medium buffered with HEPES during the ICSI procedure. MAIN OUTCOME MEASURE(S): Fertilization rate, degeneration rate, triploid rate, cleavage rate, embryo quality, pregnancy rate, implantation rate, and abortion rate. RESULT(S): Oocytes treated with a HEPES-buffered medium showed a statistically significant higher rate of triploid and degenerated oocytes after fertilization with ICSI compared with oocytes treated with a medium without HEPES. The embryos obtained from oocytes microinjected with a HEPES-buffered medium showed a statistically significant higher rate of highly fragmented embryos compared with the controls. Pregnancy rate and implantation rate were statistically significantly lower in the patient group with oocytes treated with the HEPES-buffered medium. The other parameters evaluated did not show any statistically significant differences. CONCLUSION(S): Our study showed that the use of media buffered with HEPES, during the microinjection of sperm into the oocytes, is detrimental for IVF outcome and should be avoided.

Short versus long gonadotropin-releasing hormone analogue suppression protocols for superovulation in patients > or = 40 years old undergoing intracytoplasmic sperm injection.

OBJECTIVE: To determine whether the short or long protocol for controlled ovarian hyperstimulation works better in older patients undergoing IVF. DESIGN: Controlled, randomized study. SETTING: A single private IVF center. PATIENT(S): Two hundred twenty infertile women aged > or = 40 years undergoing IVF. INTERVENTION(S): At their first IVF cycle, the women were randomized into two study groups according to a computer-generated number sequence: 110 patients were treated with a long protocol, and the other 110 were treated with a short protocol for controlled ovarian hyperstimulation. MAIN OUTCOME MEASURE(S): Days of stimulation, E2 level at the day of hCG administration, amount of FSH administered, number of oocytes collected, number of embryos obtained, pregnancy rate, implantation rate. RESULT(S): Patients treated with a long protocol showed a significantly higher number of oocytes retrieved, a higher number of embryos obtained, and a higher pregnancy rate, both for cycle and transfer, compared with the short-protocol patients. The other parameters evaluated did not show any statistically significant differences. CONCLUSION(S): Our study showed that the long protocol performed better than the short protocol in older women. Our findings demonstrated that flare-up in older women might be detrimental.

A controlled trial of natural cycle versus microdose gonadotropin-releasing hormone analog flare cycles in poor responders undergoing in vitro fertilization.

OBJECTIVE: To determine the efficacy of natural-cycle IVF compared with controlled ovarian hyperstimulation in poor responders. DESIGN: Randomized, controlled study. SETTING: Private center for assisted reproduction. PATIENT(S): One hundred twenty-nine women who were poor responders in a previous IVF cycle. INTERVENTION(S): Fifty-nine women underwent 114 attempts of natural-cycle IVF, and 70 women underwent 101 attempts of IVF with controlled ovarian hyperstimulation with microdose GnRH analog flare. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved, pregnancy rate (PR) per cycle, PR per transfer, and implantation rate. RESULT(S): The poor responders treated with natural-cycle IVF and those treated with micro-GnRH analog flare showed similar PRs per cycle and per transfer. The women treated with natural-cycle IVF showed a statistically significant higher implantation rate (14.9%) compared with controls (5.5%). When subdivided into three groups according to age (or=36-39 years, >or=40 years), younger patients had a better PR than the other two groups. CONCLUSION(S): In poor responders, natural-cycle IVF is at least as effective as controlled ovarian hyperstimulation, especially in younger patients, with a better implantation rate.

Number of embryos transferred and implantation.

Multiple pregnancies are considered the most frequent and serious complication of assisted reproduction technology. To reduce the frequency of multiple pregnancies, several centers have adopted a policy of reducing the number of embryos transferred in the uterus, suggesting single embryo transfer. Even though a significant number of papers have been published on this issue, no general consensus exists on how many embryos to replace in the uterus and at which cleavage stage. We conducted a retrospective study on cycles performed throughout 2003, analyzing the relation between the number of embryos transferred and the pregnancy and implantation rates, evaluating also the role of the woman's age. No differences were found among the groups except in one-embryo transferred women, which were mostly natural cycles, for estradiol levels, number of mature oocytes retrieved, number of top quality embryos, and pregnancy rate. The implantation rate was significantly higher in the two-embryo transfers versus three-embryo transfers. We found higher pregnancy and implantation rates with similar multiple pregnancy rates in patients where only two embryos were transferred versus three embryos transfer when women were less than 35 years old. In women aged less than 35 years, which in turn have the higher expectancy of successful pregnancy and also the higher risk of multiple pregnancy, the single embryo transfer is a suitable choice for these patients.

Successful paternity with microassisted fertilization after total body irradiation-based conditioning for autologous bone marrow transplantation.

We present the case of a 20-year-old man with acute lymphoblastic leukemia who received chemotherapy with vincristine, adriamycin, cyclophosphamide, methotrexate, teniposide (VM-26), and bleomicin, followed by an autologous bone marrow transplantation after total body irradiation (TBI)-cyclophosphamide-based conditioning regimen. At 14 years, despite the severe oligoasthenospermia, he fathered a healthy child by assisted reproductive technique (ART) consisting in controlled ovarian hyperstimulation of the patient's wife, transvaginal ovum pick up and microinjection of the ovum with a previously isolated sperm cell from the patient (intracytoplasmatic sperm injection, ICSI). As far as we know, that is the first documented case of successful paternity using microassisted fertilization with ICSI technique in a patient submitted to TBI-based bone marrow transplantation.

Follicular fluid adrenomedullin concentrations in spontaneous and stimulated cycles: relationship to ovarian function and endothelin-1 and nitric oxide.

The objective of this study was to determine concentration of adrenomedullin (AM) in follicular fluid and whether a correlation exists between AM and nitric oxide (NO) or endothelin-1 (ET-1) levels in follicular fluid, serum 17beta-estradiol or other parameters of ovarian function in spontaneous and gonadotrophin stimulated ovarian cycles. Follicular fluid samples were obtained at oocyte retrieval from 50 women who underwent an in vitro fertilization (IVF) program: 40 undergoing ovarian hyperstimulation with recombinant FSH and 10 had spontaneous ovarian cycles. AM, ET-1, and NO were detected in all of the follicular fluid samples and their concentrations were similar in spontaneous and stimulated cycles. In patients undergoing ovarian stimulation, follicular fluid AM levels correlated with serum 17beta-estradiol concentration. No correlation was found between follicular AM concentration and parameters of ovarian function. Similarly, no relationship was observed between ET-1, NO, and AM follicular fluid concentrations in either spontaneous or stimulated cycles. This study suggests a possible regulatory effect of the sexual hormones on AM production by the ovary during the ovulatory process. The site of AM secretion and its function (if any), however, remain to be established.