Variation in the use of laparoscopy with inguinal hernia repairs in a sample of pediatric patients at children's hospitals.

INTRODUCTION/BACKGROUND: Metachronous contralateral inguinal hernias (MCH) occur in approximately 10% of pediatric patients following unilateral inguinal hernia repairs (UIHR). Laparoscopic evaluation of the contralateral internal ring is a method of identifying high-risk individuals for prophylactic contralateral exploration and repair. OBJECTIVE: The objective of this study was to assess variation in utilization of diagnostic laparoscopy, and report costs associated with the evaluation of a contralateral patent processus vaginalis during hernia repair in pediatric hospitals. STUDY DESIGN: The Pediatric Health Information System database was searched to identify outpatient surgical encounters for pediatric patients with a diagnosis of inguinal hernia during a 1-year period (2014). Records were identified that contained diagnostic codes for unilateral or bilateral inguinal hernia in combination with a procedure code for open hernia repair with or without diagnostic laparoscopy. RESULTS: After exclusions there were 3952 hernia repairs performed at 30 hospitals; median age was 4 years (IQR 1-7), 78.8% were male, and 64.9% Caucasian. Three-quarters (76.7%) had UIHR, 8.6% had unilateral repairs with laparoscopy (UIHRL), 12.2% had bilateral inguinal hernia repairs (BIHR), and 2.4% had bilateral repairs with laparoscopy (BIHRL). Where laparoscopy was used, 78% resulted in a unilateral repair and 22% in a bilateral procedure. The percent of patients undergoing laparoscopy varied from 0 to 57% among hospitals, and 0-100% among surgeons. Pediatric surgeons were more than three times more likely to perform a diagnostic laparoscopy compared with pediatric urologists. Median adjusted costs were $2298 (IQR 1659-2955) for UIHR, $2713 (IQR 1873-3409) for UIHRL, $2752 (IQR 2230-3411) for BIHR, and $2783 (IQR 2233-3453) for BIHRL. Median costs varied over two-fold among hospitals ($1310-4434), and over four-fold among surgeons ($948-5040). DISCUSSION: Data suggested that <10% of patients with clinically unilateral inguinal hernias developed MCH. A negative diagnostic laparoscopy ensured that 0.9-1.31% developed MCH. However, up to 30% of patients underwent contralateral exploration/repair when diagnostic laparoscopy was used. The current study found increased costs associated with the use of laparoscopy, with considerable variation in costs among surgeons and hospitals. These data elucidate competing financial and clinical consequences associated with the use of diagnostic laparoscopy with clinically unilateral hernias. CONCLUSIONS: Variation existed in the use of laparoscopy during inguinal hernia repairs and associated costs within the current sample from children's hospitals in the United States. The additional costs of laparoscopic evaluation must be considered against the clinical utility and therapeutic consequences of identifying individuals with a higher risk of metachronous contralateral inguinal hernia.

Isolated abnormal strict morphology is not a contraindication for intrauterine insemination.

This study sought to investigate whether isolated abnormal strict morphology (<5% normal forms) and very low strict morphology (0-1% normal forms) affects pregnancy rates in intrauterine insemination (IUI). This was a retrospective study performed at an Academic Medical Center/Reproductive Medicine Center. Four hundred and eight couples were included for 856 IUI cycles. 70 IUI cycles were performed in couples with abnormal strict morphology and otherwise normal semen parameters. Outcomes were measured as clinical pregnancy rate per IUI cycle as documented by fetal heart activity on maternal ultrasound. Clinical pregnancy rate did not significantly differ between the group with abnormal strict morphology [11/70 (15.7%)] and the normal morphology group [39/281 (13.9%)]. Additionally, there was no significant difference between the pregnancy rate in the abnormal morphology group compared to that of our overall institutional IUI pregnancy rate [145/856 (16.9%)]. Furthermore, there was no significant difference between pregnancy rate in the very low morphology group [3/14 (21.4%)] compared to those with normal morphology or the overall IUI pregnancy rate. Patients with isolated abnormal strict morphology have clinical pregnancy rates similar to those with normal morphology for IUI. Even in those with very low normal forms, consideration of IUI for assisted reproduction should not be excluded.

Serum concentrations of dimeric inhibins, activin A, gonadotrophins and ovarian steroids during the menstrual cycle in older women.

The transition from regular ovarian cyclicity to menopause is associated with a rise in the circulating concentrations of follicle stimulating hormone (FSH), despite the maintenance of serum oestradiol concentrations during the perimenopause. The aim of this study was to compare the pattern of secretion of dimeric inhibins, activin A, gonadotrophins and steroids in regularly cycling women of 40-50 years with normal and raised early follicular phase serum FSH concentrations and young women (25-33 years) during the menstrual cycle. Blood samples were taken prospectively almost daily throughout the menstrual cycle. Women recruited were classified into three groups: (i) older women with normal FSH [(ON-FSH), day 3 FSH <8 mIU/ml, n = 10]; (ii) older women with raised FSH [(R-FSH), day 3 FSH >8 mIU/ml, n = 6] and (iii) young normal FSH (YN-FSH) women, age 25-32 years (n = 6). Cyclic patterns of serum inhibins and activin A were similar in the ON-FSH and YN-FSH groups. The R-FSH group had significantly lower concentrations of inhibin A prior to the luteinizing hormone (LH) surge and in the mid-luteal phase and lower concentrations of inhibin B in the early follicular phase compared with the ON-FSH group. Serum concentrations of activin A, progesterone and oestradiol were similar in all three groups. It is concluded from this study that the rise in early follicular phase serum FSH in older women is associated with a decrease in circulating concentrations of inhibin B in the early follicular phase. However, lower circulating concentrations of inhibin A in the luteal phase of the R-FSH group may also contribute to the rise in early follicular phase FSH concentrations during the menstrual cycle, although further studies with larger numbers are required to confirm this observation.

Pregnancy, autonomy and paternalism.

Modern medicine is increasingly aware of the significance of patient autonomy in making treatment choices. This would seem to be particularly important where the therapy requested was "voluntary" as in fertility treatment or cosmetic surgery. However, the Hippocratic doctrine "Primum non nocere", seems especially relevant where the treatment sought may have a low chance of a successful outcome or even be life-threatening. Mrs A's case demonstrates the difficulty faced by the physician who wants to maximise her patient's autonomy, but "Above all, do no harm".

Identification of the source of inhibins at the time of conception provides a diagnostic role for them in very early pregnancy.

PROBLEM: Early diagnosis of a complicated or poor pregnancy outcome in patients undergoing assisted reproductive technique (ART) fertility treatment could aid their counseling and management. A possible role for the inhibin superfamily as markers of early pregnancy viability was investigated. METHOD OF STUDY: To determine the source of the dimeric glycoproteins inhibin A (alpha-beta A) in early pregnancy, serial blood samples from women who became pregnant following in vitro fertilization (IVF) with fresh embryo transfer (n = 50), from women who achieved pregnancy with frozen-thawed embryos (n = 8), and from a control group of women with spontaneous conceptions (n = 7) were analyzed using a two-site enzyme-linked immunosorbent assay (ELISA). Gonadotropin-releasing hormone (GnRH) analogues are routinely used in ART treatment cycles and are recognized to be luteolytic, and hence, periconceptual administration may be deleterious to pregnancy outcome. Serum samples were obtained from 8 IVF patients who conceived during the cycle in which they had inadvertent luteal phase exposure to GnRH analogues. RESULTS: Elevated serum levels of inhibin A were detected in ongoing pregnancies from 4 weeks' gestation and increased to an initial peak at 9-10 weeks' gestation. Significantly higher levels (P < 0.05) were found in the multiple pregnancies, and nonviable clinical pregnancies had very low levels of inhibin A. Inhibin pro-alpha C was detectable at levels above normal late luteal values in singleton and multiple pregnancies arising from IVF with fresh embryo transfer. In pregnancies established without corpus luteum activity, frozen-thaw embryo replacement, the levels of pro-alpha C containing inhibins were extremely low, suggesting that the corpus luteum is the major source of the alpha monomer. In pregnancies following inadvertent periconceptual exposure to GnRH analogue, the levels of pro-alpha C were statistically significantly higher in successful pregnancies than in early pregnancy failures. CONCLUSIONS: The feto-placental unit is confirmed as the major source of inhibin A in early pregnancy, and the initially low levels and very rapid decline in inhibin A in pregnancies with embryonic failure suggest a role for this glycoprotein as a monitor of early pregnancy viability. The corpus luteum is demonstrated to be the major source of inhibin pro-alpha C in early pregnancy, and very low levels in patients with peri-implantational exposure are indicative of lytic damage and herald pregnancy failure despite luteal supplementation with progesterone.

Inhibins and activins in human ovulation, conception and pregnancy.

The activins and inhibins are glycoproteins that belong to the transforming growth factor-beta superfamily and, as such, have diverse effects at many stages during growth and development. Originally identified by their effects on follicle stimulating hormone in males and females, the recent development of specific and sensitive assays for this group of polypeptides has permitted the elucidation of their role in 'fine-tuning' the hypothalamic-pituitary-gonadal axis. This review article focuses on the roles of inhibin and activin in female reproductive physiology with reference to possible future clinical applications in the investigation of infertility and abnormal pregnancy.

Mid-follicular phase pulses of inhibin B are absent in polycystic ovarian syndrome and are initiated by successful laparoscopic ovarian diathermy: a possible mechanism regulating emergence of the dominant follicle.

The hypothalamic pulse generator of GnRH is recognized to be central to ovulatory function as evidenced by the anovulation of women with hypogonadotrophic hypogonadism due to Kallmann's syndrome or severe anorexia nervosa. LH is released from the anterior pituitary in pulses, the frequency of which is closely entrained with those of GnRH. In contrast, secretion of FSH is influenced by a number of regulatory molecules, including GnRH, estradiol, inhibin, and activin. The close temporal relationship between changes in levels of inhibin B and FSH in the mid-follicular phase suggests that the release of inhibin B by the preovulatory follicle critically regulates pituitary FSH secretion. Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders affecting ovulation, and abnormal ovarian morphology as detected by ultrasonography remains the most sensitive diagnostic marker for this disorder. The etiology of PCOS is unclear, but its effective treatment by both anti-estrogens and by exogenous FSH suggests that a primary disorder of FSH regulation may be central. To investigate the possible role of inhibin B in the pathology of PCOS, serum inhibin B levels were measured in 10 women with PCOS on cycle day 5 of a spontaneous or progestrogen-provoked bleed and compared with levels on cycle day 5 of 10 women with regular ovulatory cycles. The mean serum inhibin B levels in the PCOS patients were significantly higher at 248 (+/- 43.4) pg/mL compared with normal controls, 126 (+/- 18.6) pg/mL (P < 0.01). Ten women with clomiphene resistant PCOS and 5 normal controls consented to undergo serial blood sampling on cycle day 5. Time Series Analysis using a Fourier Transformation to analyze the power spectrum of the data revealed that in normal women there is a distinct periodicity in inhibin B levels with a clear peak detectable every 60-70 min (P < 0.05), whereas in women with ovulatory dysfunction due to PCOS, no such pattern of regular pulsatility was seen. Four women with PCOS whose anovulation was successfully treated with laparoscopic ovarian diathermy (LOD) underwent repeat venous sampling following LOD. Their serum inhibin B levels fell to the upper limit of the normal range (160 +/- 38.5) pg/mL, and pulsatility was initiated. It is possible that inhibin B pulses are being generated directly by the ovary in response to pulses of GnRH in the peripheral circulation, or indirectly in response to FSH pulses arising in the pituitary. The function of inhibin B pulses in the mid-follicular phase of the normal cycle remains to be elucidated, but the absence of the normal pulsatile pattern in women with PCOS, in conjunction with high basal levels of inhibin B arising from the multiple small follicles characteristic of the PCOS ovary, appears to reinforce the development of a large cohort of small, developmentally arrested, and ultimately atretic follicles in these patients. Initiation of normal inhibin B pulsatility by LOD in patients with polycystic ovaries appears to correlate with the post-operative onset of ovular cycles.

Measurement of inhibin and activin in early human pregnancy: demonstration of fetoplacental origin and role in prediction of early-pregnancy outcome.

To determine the source of the dimeric glycoproteins inhibin A (alpha-betaA) and activin A (betaA-betaA) in early pregnancy, we analyzed serial blood samples from women who became pregnant following in vitro fertilization (IVF) with fresh embryo transfer (ET; n = 52) and from women who achieved pregnancy with frozen-thawed embryos (n = 8). Elevated serum levels of inhibin A were detected in ongoing pregnancies from 4 wk gestation (13 days following ET) and increased to an initial peak at 9-10 wk gestation. Significantly higher levels (p < 0.05) were found in the multiple pregnancies, and nonviable clinical pregnancies had very low levels of inhibin A. Total activin A was detectable 14 days after ET (positive pregnancy test), and higher levels were associated with multiple gestations while rapidly falling levels heralded embryonic demise. The fetoplacental unit is thus confirmed as the major source of these glycoproteins. Inhibin pro-alphaC, which circulates in great excess as a functionally inactive monomer and as part of high molecular weight functional dimers, was detectable at levels above normal late-luteal values in singleton and multiple IVF arising from fresh ETs. With frozen-thawed embryo pregnancies, the levels of pro-alphaC-containing inhibins were extremely low, confirming that the corpus luteum of pregnancy is the major source of the alpha monomer. The initially low levels and very rapid decline in inhibin A in pregnancies with embryonic failure suggest a role for this glycoprotein as a monitor of early-pregnancy viability.

Circulating inhibins and activin A during GnRH-analogue down-regulation and ovarian hyperstimulation with recombinant FSH for in-vitro fertilization-embryo transfer.

OBJECTIVE: We have investigated serial changes in plasma concentrations of inhibin A, inhibin B, pro alpha C and activin A in women undergoing stimulation with recombinant FSH in 'long-protocol' down-regulated cycles of IVF treatment. DESIGN: Blood samples were collected during the entire IVF treatment cycle at points coinciding with the early follicular phase of the cycle preceding treatment, pituitary down-regulation, stimulation with recombinant FSH, ovulatory triggering, and the luteal phase of the cycle. In patients who achieved conception, blood samples were also taken during the first 2 weeks of pregnancy. All samples were analysed for inhibin A, inhibin B, pro alpha C, activin A and oestradiol. PATIENTS: Fifteen women with normal ovarian function undergoing IVF treatment with tubal factor, mild endometriosis or idiopathic infertility. RESULTS: During pituitary desensitization, both inhibin A and inhibin B were significantly (P < 0.001, P = 0.002, respectively) reduced whereas levels of pro alpha C and activin A were largely unaltered. Levels of both inhibins rose markedly (P < 0.01) during FSH stimulation and a further rise in inhibin A was detected on the day after ovulatory trigger. Levels of both inhibin A and inhibin B then fell during and after oocyte pickup and continued to fall during the luteal phase. Activin A levels rose less markedly during gonadotrophin stimulation. Statistical analysis showed a high degree of correlation between the number of follicles (> 10 mm) and serum inhibin A (r = 0.65, P < 0.01) and pro alpha C (r = 0.65, P < 0.01) concentrations during the late follicular phase. CONCLUSIONS: These results indicate that ovarian production of dimeric inhibin A and B are gonadotrophin dependent, whereas activin A may have a significant gonadotrophin independent or extra-gonadal source. Inhibin A and pro alpha C may be useful markers for monitoring the effects of gonadotrophin stimulation.

Antiphospholipid antibodies in women having in-vitro fertilization.

Antiphospholipid antibodies have an established association with pregnancy complications such as recurrent miscarriage, growth retardation, placental abruption and stillbirth but their mechanism of action is unclear. We have investigated whether antiphospholipid antibodies occur more frequently in women having in-vitro fertilization (IVF) and whether their presence is associated with the likelihood of failed implantation. We studied 240 women undergoing IVF treatment who were

Successful pregnancy outcome in a renal transplant patient following in-vitro fertilization.

Renal transplantation transforms the fertility potential of women with end-stage renal failure and the prognosis for both pregnancy outcome and continuing renal function in those patients is generally good. Currently one in 50 women become pregnant following renal transplant and it may be assumed that more would welcome the chance of biological parenthood if their fertility problems, related often to tubal damage, could be overcome. We here report our experience of treating a couple with secondary infertility with in-vitro fertilization and embryo transfer where the wife is a renal transplant recipient. We believe this is the first reported case.

A prospective randomized single-blind comparative trial of nafarelin acetate with buserelin in long-protocol gonadotrophin-releasing hormone analogue controlled in-vitro fertilization cycles.

The use of gonadotrophin-releasing hormone (GnRH) agonists to control ovulation induction cycles for in-vitro fertilization (IVF) has been shown to increase the pregnancy rate and live birth rate compared with non-analogue cycles. Different formulations of GnRH agonist are available with different routes and frequencies of administration. In this prospective study, the efficacy and safety of intranasal nafarelin and buserelin as adjunctive therapy during IVF were assessed. A total of 240 female patients were recruited to the study and in the first phase patients were randomized to receive either intranasal nafarelin 200 micrograms twice daily or buserelin 200 micrograms five times daily. In the second phase, patients received either nafarelin 400 micrograms twice daily or buserelin 200 micrograms five times daily. Nafarelin 400 micrograms and buserelin 200 micrograms both produced clinical pregnancy rates of 31% per recruit and 39% per embryo transfer. The rates for nafarelin 200 micrograms were 23 and 37% respectively. There was no statistically significant difference in pregnancy rates, by either drug or dosage. The time taken for pituitary down-regulation to be achieved was significantly longer on nafarelin 200 micrograms than on either nafarelin 400 micrograms or buserelin. The total number of days stimulation with human menopausal gonadotrophin required to reach criteria for human chorionic gonadotrophin (HCG) administration was significantly longer on buserelin than on either dose of nafarelin. Median serum oestradiol concentrations on the day of HCG administration were significantly higher on either dose of nafarelin than on buserelin.

Does isolated teratozoospermia affect performance in in-vitro fertilization and embryo transfer?

The effect of the strict classification of spermatozoal morphology on the outcome of in-vitro fertilization and embryo transfer treatment cycles has been assessed in a retrospective analysis of 2144 consecutive cycles. The patients all had a standardized long protocol gonadotrophin-releasing hormone analogue cycle, with luteal phase start, to achieve down-regulation. All treatment cycles where the sperm density was abnormal (< 20 x 10(6)/ml), or where progressive motility was abnormal (< 40%), were excluded. The study excluded treatment cycles where the oocytes inseminated did not include at least one grade 1 or grade 2 oocyte. The percentage of couples achieving the normalized results of the clinic, including median fertilization rate per patient, insemination rates, numbers of embryos transferred, rates of 'spare embryo' blastocyst formation, cumulative pregnancy rates and pregnancy outcome, were calculated. No statistically significant difference arose between the two groups of patients with regard to the percentage of patients achieving the normalized median fertilization rate or higher (group 1 with > 14% normal forms, and group 2 with > or = 4%, < or = 14% normal forms). There was a statistically significantly lower chance of achieving this rate in patients of group 3 (< 4% normal forms) (P < 0.005), but 68.6% did achieve that fertilization rate or higher. There was no statistically significant difference in any of the other end points. In conclusion, a morphological classification may be appropriate as an indicator for counselling patients with regard to treatment expectations, but its use would be seem inappropriate as an index of fertilizing potential in clinical management.(ABSTRACT TRUNCATED AT 250 WORDS)

A controlled study to assess the use of in vitro fertilization with donor semen after failed therapeutic donor insemination.

OBJECTIVE: To assess the outcome of in vitro fertilization and embryo transfer (IVF-ET) with donor semen in patients who have failed to achieve conception with therapeutic donor insemination (TDI). DESIGN: Retrospective, controlled study. SETTING: All patients were managed and treated at the in vitro fertilization unit, John Radcliffe Hospital, Oxford, United Kingdom. PATIENTS, PARTICIPANTS: Thirty-eight patients undergoing 63 cycles of IVF with donor semen were compared with a control group of patients undergoing the same treatment during the same time period for tubal disease (the subgroup with the best success rates in our program), matched for age, type of infertility (primary or secondary), and number of attempts at treatment. MAIN OUTCOME MEASURES: We compared number of follicles produced, number of oocytes retrieved, fertilization rates, number of embryos obtained, number of embryos transferred, quality of embryos transferred, blastocyst formation in sibling embryos produced, clinical pregnancy rates (PRs), pregnancy loss, and pregnancy outcome. STATISTICS: Chi-squared test statistic with Yates' correction for continuity. RESULTS: There was a statistically significant difference between the number of livebirths in the donor IVF-ET group (37) and the control group (18). The cumulative PR after four cycles for the donor IVF-ET group (83%) was statistically greater than that of the control group (59%). There was no significant difference in all other parameters compared. CONCLUSION: Patients undergoing IVF-ET with donor semen have an excellent outcome. With the decline in PR after six cycles of TDI, early recourse to IVF-ET should be considered in this group of patients.

A randomized prospective study to assess the effect of the use of home urinary luteinizing hormone detection on the efficiency of donor insemination.

A study was carried out to establish whether the use of home urinary luteinizing hormone (LH) detection to predict ovulation could decrease the number of clinic visits required for the management of a donor insemination (DI) cycle, and thus optimize use of clinic resources without adversely affecting pregnancy rates. This was a randomized prospective study carried out at a donor insemination clinic in Oxford, England. Fifty-six patients participated in the trial; 27 used home urinary ovulation detection for a total of 111 cycles and 29 had a total of 123 DI cycles managed by routine clinical methods. There was a significant reduction in the number of visits per cycle (P less than 0.001) if home kits for detection of ovulation were used. There was no significant difference in the monthly fecundity or cumulative conception rates. We conclude that the use of home urinary LH detection in donor insemination can reduce patient attendance at the clinic and optimize the use of medical resources without adversely affecting pregnancy rates.

A comparison of the transient hyperprolactinaemic stress response obtained using two different methods of analgesia for ultrasound-guided transvaginal oocyte retrieval.

Transient hyperprolactinaemia has been shown to accompany the procedure of oocyte retrieval under laparoscopic control. This study was concerned with establishing whether transvaginal oocyte retrieval was also associated with hyperprolactinaemia and whether the hyperprolactinaemic response was dependent on the method of anaesthesia/analgesia employed. Two distinct patterns were recorded. Oocyte retrieval under general anaesthesia was accompanied by a rapid rise in prolactin levels, which peaked after 40 min. Oocyte retrieval under intravenous sedation was associated with a slow rise in circulating prolactin concentrations. Significant differences in the prolactin rise between the general anaesthesia and sedation groups appeared within 10 min of the start of the procedure. It is concluded that although the surgical stress of oocyte recovery is associated with mild transient hyperprolactinaemia, most of the hyperprolactinaemic response is due to the anaesthetic.

Experience with the first 250 endometrial resections for menorrhagia.

234 patients with menorrhagia were treated hysteroscopically by transcervical resection of the endometrium (TCRE) instead of hysterectomy. 250 procedures were performed under general anaesthesia (63%) or under sedation plus local anaesthesia (38%). The endometrium was excised either totally (91%) or partially (9%) in all but one case, and 56 (22%) of the patients underwent simultaneous resection of submucous fibroids. Surgical time (range 10-100 min) varied with the gynaecologist's experience. 479 ml was the average volume of uterine irrigant absorbed by the patient. Blood loss was usually slight. Operative complications were uncommon, but 4 (2%) women sustained a uterine perforation (without serious sequelae), 7 (3%) absorbed more than 2 litres of fluid, and 1 required tamponade to control postoperative bleeding. Hospital stay was short and full recovery usual by 1-2 weeks. Menstrual symptoms improved in over 90% of the patients throughout the follow-up of up to 2 1/2 years; 27-42% of the women became amenorrhoeic at some time after total TCRE. Results were best in women greater than 35 years of age, but was not influenced by the presence of fibroids or pretreatment dysmenorrhoea. 10 (4%) women later underwent hysterectomy. Hysteroscopy 3 and 12 months after surgery revealed a small, fibrotic uterine cavity in the majority.