Vivien MacLachlan

Effect of intramural, subserosal, and submucosal uterine fibroids on the outcome of assisted reproductive technology treatment

OBJECTIVE To investigate the effect of subserosal, intramural, and submucosal fibroids on the outcome of assisted reproductive technology (ART) treatment. DESIGN A retrospective comparative study. SETTING A tertiary referral center for infertility. PATIENT(S) Treatment outcome of 106 ART cycles in 88 patients with uterine fibroids (33 subserosal, 46 intramural without cavity distortion, and 9 submucosal) was compared with that of 318 ART cycles in age-matched patients without fibroids. INTERVENTION(S) Controlled ovarian hyperstimulation and ART. MAIN OUTCOME MEASURE(S) Findings on transvaginal uterine ultrasonography performed before the initiation of treatment and pregnancy and implantation rates. RESULT(S) The pregnancy rates per transfer were 34.1%, 16.4%, 10%, and 30.1% in the patients with subserosal fibroids, intramural fibroids, submucosal fibroids and no fibroids, respectively. The implantation rates were 15.1%, 6.4%, 4.3%, and 15.7%, respectively. Both rates were significantly lower in patients with intramural fibroids than in those with subserosal fibroids or no fibroids. CONCLUSION(S) Pregnancy and implantation rates were significantly lower in the groups of patients with intramural and submucosal fibroids, even when there was no deformation of the uterine cavity. Pregnancy and implantation rates were not influenced by the presence of subserosal fibroids. Surgical or medical treatment should be considered in infertile patients who have intramural and/or submucosal fibroids before resorting to ART treatment.

Recruitment of follicles by recombinant human follicle-stimulating hormone commencing in the luteal phase of the ovarian cycle

OBJECTIVE To investigate, in patients who previously had a suboptimal ovarian stimulation cycle, the benefit of starting ovarian stimulation before the onset of menses. DESIGN Prospective, randomized, controlled study. SETTING A tertiary referral center for infertility treatment. PATIENT(S) Forty patients undergoing IVF or GIFT from whom only 3-6 oocytes were retrieved in their last cycle. INTERVENTION(S) Recombinant human FSH was administered before the onset of the menstrual period (experimental group) or in the early follicular phase after the onset of menses (control group). MAIN OUTCOME MEASURE(S) The number of oocytes retrieved. RESULT(S) Patients in the experimental group were ready for oocyte retrieval on menstrual cycle day 11 instead of cycle day 14. The number of oocytes retrieved was not significantly different between the two groups. CONCLUSION(S) Poor responders do not benefit from commencing recombinant human FSH therapy in the luteal phase.

A controlled study of luteinizing hormone-releasing hormone agonist (buserelin) for the induction of folliculogenesis before in vitro fertilization.

Treatment with clomiphene citrate and human menopausal gonadotropin (HMG) is often used to induce folliculogenesis before in vitro fertilization, but not all women have an adequate response. It has been hypothesized that abnormally high levels of luteinizing hormone (LH) may contribute to the reduced folliculogenesis. We therefore performed a controlled, open trial in which treatment with buserelin, an agonist of luteinizing hormone-releasing hormone citrate and HMG in 44 consecutive women in whom no oocytes or only one had been produced by standard treatment with clomiphene and HMG. Twenty-nine women received buserelin with HMG, and 15 received clomiphene citrate with HMG. The median number of oocytes per patient recovered from those who received buserelin with HMG was 4 (range, 0 to 19), as compared with 0 (range, 0 to 5) in those who received clomiphene citrate with HMG. The fertilization rates of oocytes recovered from both groups of patients were similar (75.8 percent and 76.5 percent, respectively). Fifty-four percent of patients given buserelin with HMG underwent triple-embryo transfer, as compared with 13 percent of those given clomiphene citrate with HMG. Pregnancy (n = 3) occurred only among the patients receiving buserelin with HMG. In the buserelin-HMG group, significantly fewer oocytes were recovered from patients with occult ovarian failure (infertility and elevated follicular-phase levels of follicle-stimulating hormone, with regular menses) (median, 1; range, 0 to 4) than from those with other causes of infertility (median, 8; range, 0 to 19). Our data suggest that, except in women with occult ovarian failure, buserelin and HMG improve embryologic and clinical outcomes in patients with previously unsatisfactory stimulation of the ovaries for in vitro fertilization.

Different influence of incongruent follicular development on in vitro fertilization–embryo transfer and gamete intrafallopian transfer pregnancy rates

OBJECTIVE To compare the influence of incongruent (asymmetric) follicular development on treatment outcome in IVF-ET and GIFT cycles. DESIGN A retrospective comparative study. SETTING Tertiary referral center for infertility. PATIENT(S) Five hundred forty-three consecutive assisted reproduction cycles (428 IVF-ET and 115 GIFT) in 422 infertile patients. INTERVENTION(S) Controlled ovarian hyperstimulation (COH) and IVF-ET or GIFT. MAIN OUTCOME MEASURE(S) The incongruity ratio as a parameter of the asymmetry in follicular development and pregnancy rate (PR). RESULT(S) For GIFT cycles, the PRs were 37.8% and 15.7% in cycles with congruent and incongruent follicular development, respectively. However, for IVF-ET cycles, the PR was not affected by incongruent follicular development: 28.2% and 29.0%, respectively. An inverse relationship was observed between the degree of incongruity and the estimated probability of pregnancy in GIFT cycles but not in IVF-ET cycles. Neither the side of the dominant ovary nor the degree of incongruity were consistent in consecutive cycles. CONCLUSION(S) Incongruent follicular development during COH has a significantly negative influence on the outcome of GIFT cycles but not on the outcome of IVF-ET cycles. The reason for this difference is not clear. We recommend considering IVF-ET instead of GIFT if incongruent follicular development occurs.

Sex ratio and birth weights of infants born as a result of blastocyst transfers compared with early cleavage stage embryo transfers

OBJECTIVE To analyze the birth weights and sex ratio of infants born as a result of blastocyst transfer and compare them with data resulting from the transfer of early-cleavage stage embryos. DESIGN Retrospective analysis. SETTING Monash IVF (private in vitro fertilization clinic). PATIENTS(S) One hundred twenty-five infertile patients who became pregnant after IVF procedures involving blastocyst transfer. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Sex ratio and birth weights of infants born after blastocyst transfer. RESULT(S) The sex ratio of 129.6 for infants born after blastocyst transfer was not significantly different from the sex ratio calculated from data compiled by NPSU for births resulting from early cleavage stage embryo transfers at Monash IVF (100.6) and all other assisted conception units in Australia and New Zealand (97.9). No differences were observed in the combined mean birth weight of male and female infants born as a result of blastocyst transfers and early-cleavage stage embryo transfers. CONCLUSION(S) There is no evidence of abnormal fetal growth or a shift in the sex ratio for infants born as a result of blastocyst transfer when compared with the case of births resulting from early cleavage stage embryo transfers within our unit or all other assisted conception units in Australia and New Zealand.

Replacement of one selected embryo is just as successful as two embryo transfer, without the risk of twin pregnancy

The transition of in vitro fertilization from research to standard clinical practice has, to a great extent, been as a result of the use of controlled ovarian hyper stimulation. A disadvantage of the availability of multiple embryos has been the replacement of several embryos leading to an epidemic of multiple pregnancies. This retrospective review of 2606 fresh embryo transfers between 2001 and 2003, where either one or two selected embryos were replaced from an available cohort of at least four, shows that single embryo transfers have a similar pregnancy rate without the risk of multiple pregnancy.

Can you ever collect too many oocytes

STUDY QUESTION Does the chance of pregnancy keep improving with increasing number of oocytes, or can you collect too many? SUMMARY ANSWER Clinical pregnancy (CP) and live birth (LB) rates per embryo transfer varied from 10.2 and 9.2% following one oocyte collected to 37.7 and 31.3% when >16 oocytes were collected. Regression modelling indicated success rates increased or at least stayed the same with number of oocytes collected. WHAT IS KNOWN ALREADY It has been suggested that if >15 oocytes are collected, the success rate for fresh embryo transfers decreases. As this is counterintuitive, as more oocytes should result in more embryos, with a better choice of quality embryos, we decided to analyse the recent experience in a busy IVF unit. STUDY DESIGN, SIZE DURATION A retrospective analysis of clinical pregnancy and live birth outcome, with respect to number of oocytes collected at Monash IVF for the 2-year period between August 2010 and July 2012, where patients under the age of 45 years underwent a fresh embryo transfer. This included 7697 stimulated cycles for IVF and ICSI. PARTICIPANT/MATERIALS, SETTING, METHODS Statistical analysis involved data tables and graphs comparing oocyte number with outcome. Results of women who had their first oocyte collection with an embryo transfer within the reference period were analysed by logistic regression analysis including other covariates that might influence pregnancy outcome. Analysis was also carried out of all the 7679 oocyte collections undertaken, resulting in fresh embryo transfers by generalized estimating equations to allow for the within subject correlation in outcomes for repeated treatments. MAIN RESULTS AND THE ROLE OF CHANCE The number of oocytes collected varied from 1 to 48. Clinical pregnancy and live birth rates per embryo transfer varied from 10.2 and 9.2% when only one oocyte was collected to 37.7 and 31.3% when >16 oocytes were collected. Regression modelling indicated success rates increased or at least stayed the same or with the number of oocytes collected. The percentage of women with embryos cryopreserved increased from under 20% with <4 oocytes collected to over 70% with >16 oocytes collected. There was a slight increase (from 18 to 22%) in oocyte immaturity and a more marked increase (from 0 to 3%) in cancelling fresh transfers to prevent Ovarian Hyperstimulation Syndrome (OHSS) with increase in number of oocytes collected above 16. The results of this study suggest that you cannot collect too many oocytes as both clinical pregnancy and live birth rates do not decrease with high numbers of oocytes collected. However, once >15 oocytes are collected, everything gets quite uncertain. LIMITATIONS, REASONS FOR CAUTION As the data become sparse above 15 oocytes, we could not demonstrate a significant increase in pregnancy rates above this number. Larger studies would be required to answer the question whether there is a plateau, or rates continue to increase. The negative of aggressive stimulation to produce many oocytes is that the risk of OHSS increases, and this is the most serious complication of ovarian stimulation. STUDY FUNDING/COMPLETING OF INTERESTS No funding was required. There is no conflict of interest, except that G.K., V.M. and C.M. are shareholders in Monash IVF Pty Ltd.

Outcome of pregnancies achieved by in vitro fertilisation techniques and diagnosed as twins at the 6 week ultrasound.

Background: To bring the success rate of in vitro fertilisation (IVF) procedures to an acceptable level, multiple embryos have historically been replaced. This has resulted in an ‘epidemic’ of multiple births. The pendulum has now swung full circle and the number of embryos transferred is now being limited. Such high numbers of IVF twins will not be produced in the future.

The success rate of IVF has significantly improved over the last decade.

To demonstrate that success rates with in vitro fertilisation (IVF) have been improving despite decreasing the number of embryos transferred.