Ian S. Tummon

Randomized controlled trial of superovulation and insemination for infertility associated with minimal or mild endometriosis

OBJECTIVE To evaluate the efficacy of superovulation and IUI versus no treatment for infertility associated with minimal or mild endometriosis. DESIGN Randomized trial. SETTING(S) London Health Sciences Centre, University Campus, The University of Western Ontario, London, Ontario; and Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada. PATIENT(S) Three hundred eleven cycles in 103 couples in whom minimal or mild endometriosis was the sole identified subfertility factor. INTERVENTION(S) Superovulation with FSH and IUI. MAIN OUTCOME MEASURE(S) Live birth. RESULT(S) Live birth followed 14 of 127 (11%) superovulation and IUI cycles and 4 of 184 (2%) no-treatment cycles. The odds ratio was 5.6 (95% confidence interval 1.8 to 17.4) in favor of superovulation and IUI. CONCLUSION(S) Treatment with superovulation and IUI was associated with superior outcome both by crude live-birth rates and proportional hazard analysis.

Future in vitro fertilization pregnancy potential of women with variably elevated day 3 follicle-stimulating hormone levels

OBJECTIVE To determine the IVF-ET pregnancy potential of women with variably elevated day 3 FSH. DESIGN Cohort evaluation of 1,868 consecutive IVF-ET cycles January 1991 to December 1994. SETTING University hospital infertility unit. PATIENTS Four cohorts of couples were defined based on day 3 FSH determinations with an arbitrary threshold of 20 mIU/mL, only > or = 20 mIU/mL, always < 20 mIU/mL, current < 20 mIU/mL but one previous > or = 20 mIU/mL, and current < 20 mIU/mL but two or more previous > or = 20 mIU/mL (conversion factor to SI unit, 1.00). INTERVENTION In vitro fertilization-embryo transfer. MAIN OUTCOME MEASURE Fetal heart activity on luteal day 40 transvaginal ultrasound. RESULTS No pregnancies occurred in 53 cycles with day 3 FSH only > or = 20 mIU/mL. In 1,750 women whose day 3 FSH levels were always < 20 mIU/mL, the pregnancy rate (PR) per cycle was 16.5%. In 54 cycles in which day 3 FSH was > or = 20 one time only, but < 20 mIU/mL during the treatment cycle, the PR was 5.6%. In 11 cycles where two or more previous FSH determinations were > or = 20 mIU/mL but with a current day 3 FSH < 20 mIU/mL, no pregnancies occurred. CONCLUSION Our data leads us to the conclusion that day 3 FSH determination precede every IVF cycle and that cycles with FSH > or = 20 mIU/mL be canceled. It also suggests that women with two previous elevations of day 3 FSH be discouraged from future IVF cycles. The 5.6% pregnancy per cycle with one previously elevated FSH warrants extreme pessimism in discussion of further cycles.

Memory complaints associated with the use of gonadotropin-releasing hormone agonists: a preliminary study

OBJECTIVES To study the effect of GnRH agonist (GnRH-a) treatment on memory and to assess the role of psychological factors. DESIGN A randomized prospective study. SETTING An academic teaching hospital. PARTICIPANTS Women with endometriosis and infertility or endometriosis alone. MAIN OUTCOME MEASURES Memory Observation Questionnaire, Profile of Mood States, Health Concerns scale, a weekly diary of adverse effects. RESULTS Perceived memory functioning decreased during GnRH-a administration and by the final week of treatment 44% of women reported moderate to marked impairment in comparison to community norms. Prospective memory was most affected and withdrawal of GnRH-a treatment resulted in a return to normal memory functioning. Impairment was not related to excessive health concerns or mood changes and was uncorrelated with other adverse effects. CONCLUSIONS Memory disruption may be a more common side effect of GnRH-a treatment than currently is recognized. Problems were temporary and more likely a result of rapid estrogen depletion than a consequence of mood, somatic distress, or personality factors.

Randomized, prospective comparison of luteal leuprolide acetate and gonadotropins versus clomiphene citrate and gonadotropins in 408 first cycles of in vitro fertilization

OBJECTIVE To compare luteal phase leuprolide acetate (LA) initiated pituitary down regulation followed by human menopausal gonadotropins (hMG) versus clomiphene citrate (CC) and hMG for follicular recruitment and oocyte maturation before in vitro fertilization (IVF). DESIGN Randomized, prospective comparison in first cycles of IVF. SETTING University Hospital, a tertiary referral center offering assisted reproductive technologies. PARTICIPANTS Participants were couples undergoing their first ever cycle of IVF and consenting to participation in the trial. RESULTS Luteal phase initiated LA/hMG was associated with a lower probability of cycle cancellation, improved folliculogenesis, and a higher probability of embryo transfer (ET) compared with CC/hMG alone. Implantation rates were not different. CONCLUSION A higher rate of ET with LA/hMG suggests that gonadotropin-releasing hormone agonist for the induction of folliculogenesis before IVF may be appropriate.

Transferring more embryos increases risk of heterotopic pregnancy

OBJECTIVES To analyze symptoms and signs that may distinguish heterotopic pregnancy from solely ectopic pregnancy (EP) after IVF. To determine if the number of embryos transferred is a risk factor for heterotopic compared with solely EP. DESIGN Retrospective cohort of 587 IVF pregnancies, 328 with distorted tubal anatomy. SETTING University Hospital, London, a referral center for Ontario provincial government-supported assisted reproductive technologies. PARTICIPANTS Couples undergoing IVF. INTERVENTION None. MAIN OUTCOME MEASURES Heterotopic pregnancy, solely EP, intrauterine pregnancy, and distorted pelvic anatomy. RESULTS Of 587 pregnancies, 7 were heterotopic pregnancies and 24 were solely EP, all in the subset of 328 women with distorted tubal anatomy. Symptoms, signs and time of diagnosis were not different between heterotopic and solely ectopic gestations. Compared with solely EP, heterotopic pregnancies were associated with transfer of more embryos. With four or more embryos transferred, the odds ratio for development of heterotopic versus solely ectopic gestation was 10.0. CONCLUSION Heterotopic pregnancy occurred in 2% of gestations after IVF, all in women with distorted tubal anatomy. Transfer of four or more embryos was a risk factor for heterotopic pregnancy.

Abbreviated endometriosis-associated infertility correlates with in vitro fertilization success

The utility of in vitro fertilization (IVF) for refractory infertility associated with endometriosis was studied by reviewing the 6-year experience with IVF and pregnancy follow-up at University Hospital, London, Ontario. Two hundred forty cycles were begun in 124 couples in whom endometriosis was the sole identified cause of infertility. In a program employing predominantly ultrasoundguided transvaginal oocyte retrieval, live birth rates were not reduced with advanced degrees of endometriosis. Live births were positively correlated with a shorter infertility duration.

Hysteroscopic Endometrial Ablation Is an Effective Alternative to Hysterectomy in Women with Menorrhagia and Large Uteri

STUDY OBJECTIVES To examine the feasibility, safety, and outcome of hysteroscopic endometrial ablation, and to determine the volume of fluid absorbed during resection versus rollerball coagulation in women with menorrhagia and large uteri. DESIGN Retrospective review (Canadian Task Force classification II-2). SETTING University-affiliated teaching hospital. PATIENTS Forty-two consecutive patients (mean +/- SD age 45.6 +/- 6 yrs) with uterine size greater than 12 weeks (cavity >12 cm). Intervention. Endometrial ablation; 26 (62%) women were pretreated to thin the endometrium. MEASUREMENTS AND MAIN RESULTS Resection was performed in 27 patients (65%) and rollerball coagulation in 15 (35%). Ablation was successfully performed in all patients in a day surgery setting. Multiple regression analysis examined the relationship of uterine size, pretreatment, procedure, and duration of surgery to amount of glycine absorbed. Glycine absorption was higher with resection than with coagulation (p = 0.04). Fluid absorption correlated with type of procedure (r = 0.32, p = 0.04) but not with duration of the procedure, uterine size, or pretreatment. One patient with uterine fibroids and one with endometrial adenocarcinoma had hysterectomy. With follow-up of 39 (95%) of 41 women (excluding the one with adenocarcinoma) for 14 +/- 2 months, 38 (93%) were very satisfied. Thirty (73%) had amenorrhea, six (15%) had hypomenorrhea (<3 pads/day), and three (7%) had eumenorrhea (<10 pads/day). CONCLUSION Hysteroscopic endometrial ablation may be a feasible, safe, and effective alternative to hysterectomy in women with menorrhagia and large uteri.

Confounding variables affecting in vitro fertilization success : a decade of experience

PurposeTo evaluate etiology of infertility, female age, ovarian response and stimulation protocol in affecting in vitro fertilization (IVF) success.MethodsRetrospective analysis was used. Computer records of all 5209 cycles initiated in 2391 couples from February 1, 1984 to December 31, 1993 were analyzed.ResultsThere were 644 intrauterine, 24 solely ectopic and 7 heterotopic pregnancies. Pregnancy rates increased with number of embryos transferred with a significant increase still found between transfer of three or four embryos. Multiple gestations also increased in association with an increasing number of embryos transferred. Pregnancy rates per cycle did not decline with repeated cycles. Reduced pregnancy rates were associated with a primary diagnosis of male infertility. Covariates associated with a better pregnancy rate were younger age of the female partner or higher peak preovulatory serum estradiol. Routine administration of GnRH-agonist was associated with a reduced cycle cancellation rate, an increase in oocytes retrieved and an improved pregnancy rate.ConclusionsCouples with male infertility and increased female age should be counselled regarding the reduced prognosis for success.

Randomized trial of partial zona dissection for male infertility

OBJECTIVES To compare IVF rates using partial zona dissection versus zona intact insemination in couples with male infertility. To analyze pregnancy rates relative to sperm characteristics, fertilization rates, and treatment. DESIGN Randomized prospective comparison of fertilization in sibling oocytes. Transfer of the three best quality embryos from one or both treatments. SETTING Department of Gynaecology and Reproductive Medicine, University Hospital, London, Ontario, Canada. PARTICIPANTS Thirty-two couples undergoing IVF with a principal diagnosis of male infertility. INTERVENTION Treatment with partial zona dissection. MAIN OUTCOME MEASURES Fertilization and pregnancy. RESULTS Fertilization rates were 26% and 9% after partial zona dissection and IVF, respectively. Polyspermy was < 1% in each treatment. There were five singleton pregnancies in 29 completed cycles, three in cycles with fertilization only by partial zona dissection and two in cycles with both partial zona dissection and IVF fertilization. There were no pregnancies after fertilization by IVF only. Stepwise logistic regression analysis indicated that pregnancy was related to partial zona dissection, initial sperm concentration, and total acrosin activity. CONCLUSION Partial zona dissection was associated with minimal polyspermic fertilization and higher normal fertilization rates than sibling oocytes treated by modified IVF. Pregnancy occurred only after transfer of embryos from partial zona dissection or combined partial zona dissection and IVF.

Success, Safety, Single Sperm: Intracytoplasmic Sperm Injection Today

Abstract Objectives: To assess the indications and merits of intracytoplasmic sperm injection. To consider the affordability of intracytoplasmic sperm injection. To consider the hazards of intracytoplasmic sperm injection. Design: Silver Platter Review of English language citations for intracytoplasmic sperm injection from 1990 to 1996, hand searching abstracts and journals. Conclusions: Intracytophsmic sperm injection is a vital innovation for treating male infertility. Intracytoplasmic sperm injection is complex and costly. Rational use of intracytoplasmic sperm injection depends on accurate diagnostic andrology. Data are inadequate to assess the risks of congenital malformations accurately. Even in young women there may be a one percent risk of sex chromatin abnormalities.