Among patients treated with FSH and GnRH analogues for in vitro fertilization, is the addition of recombinant LH associated with the probability of live birth? A systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to assess whether the addition of recombinant luteinizing hormone (LH) increases live birth rate, among patients treated with follicle stimulating hormone (FSH) and gonadotrophin-releasing hormone (GnRH) analogues for in vitro fertilization (IVF). Eligible studies were randomized controlled trials (RCTs) answering the research question that contained sufficient information to allow ascertainment of whether randomization was true and whether equality was present between the groups compared, regarding baseline demographic characteristics, gonadotrophin stimulation protocol, number of embryos transferred and luteal phase support administered. A literature search identified seven RCTs (701 patients) that provided the information of interest, among which five reported agonist and two antagonist cycles. The reported outcome measure, clinical pregnancy, was converted to live birth using published data in one study. No significant difference in the probability of live birth was present with or without rLH addition to FSH (odds ratio [OR]: 0.92, 95% confidence interval (CI): 0.65-1.31; P = 0.65). This finding remained stable in subgroup analyses that ordered the studies by dose of rLH added, the type of analogue used to inhibit premature LH surge, the time rLH was added during the follicular phase, the age of patients analysed, the presence of allocation concealment and by the way the information on live birth was retrieved. In conclusion, the available evidence does not support the hypothesis that the addition of recombinant LH increases the live birth rate in patients treated with FSH and GnRH analogues for IVF.

Expression of estrogen receptors alpha and beta in two uterine mesenchymal tumors after prolonged tamoxifen therapy. Report of two cases.

INTRODUCTION: Tamoxifen therapy is associated with an increased risk of endometrial carcinoma, and possibly uterine sarcomas. Little is known about hormone receptor expression in mesenchymal tumors of the uterus after tamoxifen therapy. CASES: The cases of two patients with uterine mesenchymal tumors after prolonged tamoxifen therapy due to breast cancer are presented. The expression of estrogen receptors alpha (ERalpha) and beta (ERbeta) and progesterone receptors (PR) was studied immunohistochemically in both cases. Both tumors were negative for ERalpha and positive for ERbeta. In the first case the tumor was negative for PR, while in the second only 20% of nuclei were PR-positive. CONCLUSIONS: Consistent with previous studies, uterine mesenchymal tumors after tamoxifen therapy do not express ERalpha. The results of the present report provide for the first time evidence that tamoxifen might exert a stimulatory effect on the uterus, at least during tumor progression, through ERbeta but not through ERalpha.

Association of oestrogen receptor alpha polymorphisms and androgen receptor CAG trinucleotide repeats with male infertility: a study in 109 Greek infertile men.

This study was performed to examine the contribution of genetic polymorphism of oestrogen and androgen receptor (AR) genes in male infertility. We have studied in total 173 Greek men, 109 infertile patients and 64 controls (group A). Patients were divided in to three subgroups: group B (n=29) with idiopathic moderate oligospermia, group C (n=42) with azoospermia or idiopathic severe oligospermia and group D (n=38) with azoospermia or oligospermia of various known aetiologies. All patients and controls were genotyped for two polymorphisms of the oestrogen receptor alpha (ERalpha) gene and also for the (CAG)n repeat length polymorphism of the X-linked androgen receptor (AR)gene. The control group had statistically significant difference from group C regarding the XbaI polymorphism of ERalpha gene. Despite the fact that we did not observe any statistically significant differences in the mean and range of the CAG repeat number, the frequency of the higher repeats of the nucleotide repeat sequence (CAG)n of the AR gene was 2-4 times higher in groups B and C compared with the control group A. Our results indicate that both ERalpha and AR gene play significant role in male fertility. It is possible that a synergy may exist between unfavourable genotypes of these two genes in male infertility.

Interleukin-1 beta and tumor necrosis factor-alpha in normal/infertile men.

Cytokines play an important role in intercellular communications. Human sperm contains a wide spectrum of cytokines. such as interleukin-1 beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha). Their effects on semen quality are subject to debate. The aim of this study was to determine concentrations of IL-1beta and TNF-alpha in normal fertile men and in different groups of male infertility in an attempt to clarify the physiology and suggest possible clinical uses. Sixty-six subfertile male patients with varicocele (n = 22). infection of accessory genital glands (n = 14), varicocele plus infection (n = 4), chronic epididymitis (n = 8). post-renal transplantation status (n = 5), idiopathic oligoasthenoteratospermia (n = 9), cryptorchidism (n = 1), and homozygous beta-thalassemia (n = 3) as well as 5 male controls were studied through history, physical examination, spermiograms, plasma basal hormonal levels, and IL-1beta and TNF-alpha levels in seminal fluid. There was no significant statistical difference regarding IL-1beta and TNF-alpha among fertile men and subfertile patients of any cause. 1L-1beta and TNF-alpha were in tight positive correlation (p<.001). Determination of IL-1beta and TNF-alpha does not provide useful information in male routine infertility workup. Nevertheless, a better understanding of these mediators in semen of normal men and infertile patients may contribute to a new approach to the management of male infertility.

Congenital obstructive azoospermia in a man with Marfan syndrome.

OBJECTIVE: To present a case of Marfan syndrome and concurrent congenital obstructive azoospermia. DESIGN: Case report. SETTING: Tertiary-care academic hospital. PATIENT(S): A man with Marfan syndrome and obstructive azoospermia. INTERVENTION(S): The patient was evaluated for azoospermia that was proved to be due to congenital absence of large segments of vas deferens and epididymis bilaterally. MAIN OUTCOME MEASURE(S): Evaluation for testicular sperm extraction and ICSI procedure. RESULT(S): The patient is a candidate for testicular sperm extraction and ICSI. CONCLUSION(S): The Marfan syndrome and azoospermia may be associated in sporadic cases.

Ambiguous genitalia, 45,X/46,XY mosaic karyotype, and Y chromosome microdeletions in a 17-year-old man.

OBJECTIVE: To describe clinical and laboratory features of a patient with 45,X/46,XY mosaic karyotype and Y chromosome microdeletions and to discuss the diagnostic problems in his management. DESIGN: Case report. SETTING: University department. PATIENT(S): A 17-year-old man with ambiguous genitalia, 45,X/46,XY mosaic karyotype, and Y chromosome microdeletions. INTERVENTION(S): Testicular ultrasonography, karyotype, open testicular biopsy, polymerase chain reaction (PCR) screening for cystic fibrosis, PCR screening for Y chromosome microdeletions in peripheral blood and testicular tissue, and reverse transcriptase PCR in testicular tissue for Y chromosome microdeletions. MAIN OUTCOME MEASURE(S): Avoidance of dissemination of testicular cancer. RESULT(S): The patient was referred for bilateral orchiectomy. CONCLUSION(S): 45,X/46,XY mosaic karyotype is associated with a broad spectrum of phenotypes that includes female with Turner syndrome, male with mixed gonadal dysgenesis, male pseudohermaphroditism, and apparently normal male. Microdeletions of the long arm of the Y chromosome may be associated with Y chromosomal instability, leading to formation of 45,X cell lines. 45,X/46,XY males carry an increased risk for gonadal tumors and must be followed closely.

Can maturation arrest occur at the stage of spermiogenesis?

This article attempts to clarify the pathological condition during which the maturation of the germinal epithelium is unable to evolve beyond a certain stage and is characterized as maturation arrest. Emphasis is given to the histological entity named spermiogenic arrest.

Acrosome reaction: methods for detection and clinical significance.

The present article reviews the methods for detection and the clinical significance of the acrosome reaction. The best method for the detection of the acrosome reaction is electron microscopy, but it is expensive and labour-intensive and therefore cannot be used routinely. The most widely used methods utilize optical microscopy where spermatozoa are stained for the visualization of their acrosomal status. Different dyes are used for this purpose as well as lectins and antibodies labelled with fluorescence. The acrosome reaction following ionophore challenge (ARIC) can separate spermatozoa that undergo spontaneous acrosome reaction from those that are induced, making the result of the inducible acrosome reaction more meaningful. Many different stimuli have been used for the induction of the acrosome reaction with different results. The ARIC test can provide information on the fertilizing capability of a sample. The ARIC test was also used to evaluate patients undergoing in vitro fertilization since a low percentage of induced acrosome reaction was found to be associated with lower rates of fertilization. The cut-off value that could be used to identify infertile patients is under debate. Therapeutic decisions can also be made on the basis of the value of the ARIC test.

Procalcitonin: does it play a role in male reproduction?

OBJECTIVE: To investigate the presence or absence of procalcitonin in the seminal plasma of both normal and subfertile men. DESIGN: Controlled clinical study. SETTING: Academic research environment. PATIENT(S): Healthy male volunteers and subfertile men with varicocele or infection of the male accessory glands. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Seminal plasma procalcitonin determinations. RESULT(S): Seminal plasma procalcitonin levels from subfertile men were not significantly different from those found in healthy volunteers. CONCLUSION(S): Although procalcitonin can be detected in the seminal plasma, these preliminary results indicate that it cannot be used as a diagnostic marker.

Leptin levels in maternal and cord serum: relationship with fetal development and placental weight.

OBJECTIVE: To test the hypothesis that the circulating levels of leptin in the maternal and cord serum correlate with the birthweight of the newborns and with the weight of the placenta. METHODS: In a population of 85 women from northern Greece who gave birth to an equal number of full-term infants, we calculated the concentration of leptin in the maternal serum as well as in the cord serum, right after delivery, by using an immunoradiometric assay. The correlation between these values, the maternal BMI before pregnancy and at the time of delivery, the neonatal BMI, Ponderal Index, and the placental weight was studied. RESULTS: Mean maternal leptin showed a statistically significant difference from mean cord serum leptin (14.7 and 7.07 ng/ml, respectively) and was positively correlated to the maternal BMI at the time of delivery (r = 0.3, P = 0.016), but not to neonatal BMI. A positive correlation between the mean cord serum leptin and the BMI of the neonates (r = 0.26, P = 0.031 ) was found. There was no correlation between the maternal BMI at the time of delivery and the neonatal BMI. Similarly, no correlation could be established between the placental weight and the levels of leptin in the maternal or in the cord serum but a positive correlation between placental weight, neonatal BMI and weight, and mothers' BMI was observed. Finally, although a noteworthy difference between the mean leptin levels of neonates of two different sexes was observed (male 5.9 ng/ml, female 7.8 ng/ml), that difference never reached a statistically significant level. CONCLUSIONS: The maternal leptin level could not be used as a reliable marker of fetal growth but a positive correlation between cord serum leptin and fetus growth is suggested.

Spontaneous pregnancy following therapeutic approach of an infertile man with aspermia/obstructive azoospermia.

The combination of aspermia and obstructive azoospermia in the same infertile man is a rather rare entity. In the case reported here, all diagnostic criteria as well as subsequent recovery following two operations are compatible with an inflammatory origin. In such cases assisted reproduction should be recommended. However, in this case, an early spontaneous pregnancy rendered this unnecessary.

Effect of treatment with GnRH agonists on new markers of bone metabolism.

To assess the utility of new markers in monitoring bone turnover during treatment with GnRH agonists, alkaline phosphatase (total and bone specific) and urinary N-telopeptides were measured. 16 women undergoing treatment with GnRH agonists for endometriosis or leiomyomas were studied before and 3 months after the onset of treatment. N-telopeptide levels increased significantly (44% of baseline, p < 0.05). Bone specific alkaline phosphatase (BALP), measured with a new ELISA assay, was more elevated (40% of baseline, p = 0.001) than total ALP (15% of baseline, p < 0.001). In conclusion, in estrogen deficiency states, urinary N-telopeptide measurements provide a quantitative measure of bone resoption. In the assessment of bone formation, BALP determination is move sensitive than total ALP and this may be clinically useful.

Therapeutic approach of immotile cilia syndrome by intracytoplasmic sperm injection: a case report.

OBJECTIVE: To present a case of immotile cilia syndrome, a very rare cause of male infertility and to evaluate the role of the recently suggested treatment by intracytoplasmic sperm injection (ICSI). DESIGN: Case report. SETTING: Tertiary-care academic hospital. PATIENT(S): One man with immotile cilia syndrome, showing no motile spermatozoa despite normal morphology and viability. INTERVENTION(S): The patient's partner underwent two cycles with IVF of the oocytes achieved by ICSI. MAIN OUTCOME MEASURE(S): Evaluation of ICSI procedure in cases of immotile cilia syndrome. RESULT(S): Thirty-three percent of the oocytes were fertilized and subsequently divided enabling ET in both cycles. CONCLUSION(S): Intracytoplasmic sperm injection seems to represent a promising approach to the problem of infertility in men with immotile cilia syndrome.

Azoospermia: clinical, hormonal, and biochemical investigation.

The aim of this study was to evaluate the clinical, hormonal and biochemical characteristics of infertile men with azoospermia. A total of 187 azoospermic out of 2610 infertile men (7.2%) were studied. Mean testicular volume and basal plasma levels of FSH were the most useful parameters concerning the evaluation of azoospermia. Basal plasma levels of LH and T were useful only in azoospermic men with hypogonadism, whereas plasma PRL levels, semen volume, and seminal plasma fructose levels were not found to be of common use except in selected cases.

Pituitary-testicular axis in men with beta-thalassaemia major.

Delayed puberty and hypogonadism are frequently observed in patients with homozygous beta-thalassaemia. We evaluated the pituitary-testicular axis in 30 thalassaemic men, aged from 17 to 35 years who were regularly transfused and underwent chelation therapy, while emphasis was given to pituitary reserves of gonadotrophins and the correlation of hormones with serum ferritin (SF). The investigation included endocrinological examination, evaluation of serum basal levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), free testosterone and gonadotrophin-releasing hormone (GnRH) test and also spermiograms. According to the results, patients were divided into three groups: group A, which included 18 eugonadal patients with moderately elevated SF, group B which included six patients who had hypogonadotrophic hypogonadism and excessive elevation of SF, and group C, which included six patients characterized as intermediate, with regard to sexual maturation and SF levels. In conclusion, beta-thalassaemia major leads to variable pituitary iron overload and thus hypophyseal damage. This endocrine disturbance is becoming less frequent nowadays with early and intensive chelation therapy.

Evaluation of different ovarian stimulation protocols for in vitro fertilization.

In this study we evaluated retrospectively the efficacy of five different ovarian stimulation protocols in an in vitro fertilization program, in which 512 women were involved. Ovulation was induced by the following protocols: group I (271 cycles): buserelin short protocol (1 mg/day, intranasally) with human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG); group II (45 cycles): buserelin (short protocol) with pure follicle stimulating hormone (p-FSH)/hMG/hCG; group III (24 cycles): clomiphene citrate (100 mg/day) with hMG/hCG; group IV (122 cycles): hMG (3 ampules/day) and hCG; group V (113 cycles): hMG/hCG and prednisolone (7.5 mg/day) after cycle programming with oral contraceptives. The lowest cancellation rate (3.3%) was noted in group I, followed by group V (9.7%). The highest number of follicles was observed in groups I (8.3 +/- 0.3; mean +/- SEM) and V (7.8 +/- 0.5). Also, more oocytes were retrieved in group I (7.2 +/- 0.3, p < 0.001), which were of good quality based on oocyte maturity as well as on the fertilization rate, and more embryos (4.5 +/- 0.3, p < 0.05) were developed. The correlation between estradiol and the total follicular volume on the day of hCG administration was also examined in the five groups. The best correlation (r = 0.6502) was found in group I, followed by group V (r = 0.5810). Significant differences were observed in the five groups with regard to the number of hMG ampules administered (p < 0.0001, F = 15.393) and the stimulation days (p < 0.0001, F = 35.32). Sixty-six clinical pregnancies were achieved: 37 (17.5%) in group I, seven (25.9%) in group II, one (10%) in group III, ten (15.6%) in group IV and 11 (15.5%) in group V (differences were not statistically significant). In conclusion, all five protocols were satisfactory in ovarian stimulation for in vitro fertilization, and gonadotropin releasing hormone (GnRH) analogs seemed to be more advantageous by reducing the cancellation rate, enhancing the number of oocytes retrieved and embryos developed and by improving the pregnancy rates.

Effect of follicular fluid on the kinetics of human sperm acrosome reaction in vitro.

The purpose of the present study was to evaluate the kinetics of human sperm acrosome reaction in vitro using the triple stain technique. Acrosome reaction was studied in sperm samples from 16 fertile men 2, 6, and 9 h after ejaculation, following incubation in culture medium (CM; Ham's F-10), with a mixture of CM and follicular fluid (FF), or with FF only. Incubation of sperm samples without the influence of any medium served as control. The highest proportion of living acrosome-reacted sperm after a 2-h incubation period occurred in samples incubated with FF (18%), followed by samples incubated with the mixture (15.2%), and then with CM (11.8%). The proportion of living sperm that had undergone the acrosome reaction in the control group was significantly lower (5.7%, p < 0.05). After 6 h of incubation, live acrosome-reacted sperm in FF had increased to 39%, in the mixture to 35.5%, and in CM to 30.5%, whereas in the control group the increase was only 6.3% (p < 0.05). After 9 h of incubation, the percentage of living reacted sperm showed a decline compared with the percentage at 6 h. This decline was greater in samples incubated with FF (from 39 to 19.8%) than in samples incubated with the mixture (from 35.5 to 23.6%). Samples incubated in CM only showed a small decrease from 30.5 to 28.4%, while in the control group this percentage decreased from 6.3 to 2.3%. In conclusion, incubation of sperm in suitable media favorably influences the acrosome reaction, inducing an increase in the percentage of live acrosome-reacted sperm.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth hormone, oestradiol, progesterone and testosterone concentrations in follicular fluid after ovarian stimulation with various regimes for assisted reproduction.

Follicular fluid samples and oocytes were obtained from 75 women (87 cycles), who participated in an assisted conception programme. Determinations of the concentration of oestradiol, progesterone, testosterone and growth hormone were performed in all follicular fluid samples. Patients were stimulated with the following regimes: group A (24 cycles, 94 samples), human menopausal gonadotrophin (HMG) (three ampoules/day) and human chorionic gonadotrophin (HCG); group B (23 cycles, 53 samples), HMG/HCG with prednisolone (7.5 mg/day) after cycle programming with oral contraceptives; group C (40 cycles, 60 samples), buserelin with HMG/HCG. Oestradiol concentrations (mean +/- SEM) were significantly higher (P < 0.05) in group A (320.1 +/- 27.3 ng/ml) and those of growth hormone in both groups A and C (3.8 +/- 0.2 and 3.2 +/- 0.15 ng/ml, respectively), as compared to the other groups, whereas progesterone and testosterone concentrations were similar in all groups. The mean concentrations of oestradiol, progesterone, testosterone and growth hormone were significantly higher (P < 0.01) in follicular fluid with oocytes of intermediate maturity than with mature oocytes (382.5 ng/ml, 7847.5 ng/ml, 1704.5 ng/dl and 3.7 ng/ml versus 217.8 ng/ml, 5488.4 ng/ml, 1313.6 ng/dl and 2.7 ng/ml, respectively). On the other hand, only oestradiol concentrations were significantly higher in follicular fluid of fertilized compared to non-fertilized oocytes. Concentrations of the other hormones analysed, except growth hormone, were similar in follicular fluid from pregnant and non-pregnant women after assisted reproduction. Growth hormone, on the other hand, was significantly lower (P < 0.05) in follicular fluid from pregnant compared to non-pregnant women (2.8 versus 3.5 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of Hamilton-Thorn automated semen analysis system.

Sperm concentration and percentage motility values generated by the HT M-2030 system (CASA) were compared with those obtained by subjective semen analysis (SSA). Three calibrations arbitrarily designated as A, M, and D for gates and discriminators and three calibrations arbitrarily designated LI, MI, and HI for default pixel count (DPC) and default intensity (DI) were evaluated. The best correlation between CASA and SSA was observed utilizing M calibration (n = 114) with which sperm concentration was +0.3 x 10(6)/mL (r = .96) and motility was -6.3% (r = .89) compared to the values obtained by SSA. It was found that 35.9% of sperm concentration values and 34.2% of sperm motility values were within 10% of the values obtained by SSA. When sperm concentration was between 50 and 100 x 10(6)/mL the difference in motility was reduced (-3.2%) while the difference in sperm concentration was reversed (-2.6 x 10(6)/mL). LI calibration (DPC = 4, DI = 86) gave acceptable results with M calibration for sperm concentration (+2.1 x 10(6)/mL) and motility (-6.9%) compared to the values obtained by SSA. In the presence of sperm clumping, the difference between CASA and SSA was reversed for sperm concentration (+0.56 x 10(6)/mL for normal samples vs. -2.2 x 10(6)/mL for samples with clumping) and was reduced for sperm motility (-7.14% vs. -4.55%, respectively). HT M-2030 under proper calibration can be used as a rapid, objective, and reliable alternative to conventional semen analysis in routine and for research purposes.