1
P-112 Clomiphene and intrauterine insemination (IUI)—What is the best way to time insemination? Vivian Lewis, David S. Guzick. Univ of Rochester Sch of Medicine and Dentistry, Rochester, NY. Objective: Clomiphene citrate and IUI is frequently used to increase fecundity in couples with unexplained infertility. However, studies compar- ing methods of IUI timing are either retrospective or have inconsistent results. We tested the hypothesis of whether pregnancy rates in women treated with clomiphene and IUI would be different depending on whether the IUI was timed by spontaneous LH surge or hCG administration. A positive pregnancy test with rising hCG concentrations was the main out- come measure. Design: Prospective randomized clinical trial Materials/Methods: Subjects were ovulatory women with at least one patent tube and a partner or sperm donor with at least 4 million normal motile sperm per ejaculate. Randomization was performed at the baseline ultrasound, after which patients took 100 mg of clomiphene, days 5–9. The surge group began testing for LH surge using an over-the-counter kit on day 12 and underwent IUI on the day after a positive test. Patients who failed to detect a surge were dropped from the study. The hCG group returned for ultrasound starting on day 12 and received hCG when there was at least 1 follicle measuring 20 mm mean diameter and when the endometrial thick- ness was at least 8 mm with a trilaminar pattern. If the LH kit became positive before ultrasound criteria were met, IUI was scheduled accordingly. Patients remained in the same study group in subsequent months for a maximum of 3 cycles. An intent to treat approach was used in analyzing the data so that information from dropped cycles could be captured. Results: Seventy-nine patients have completed 167 cycles with a total of 19 pregnancies: 6/86 in the surge group and 13/81 in the hCG group (p .075,chi-square). There were 4 viable pregnancies among 40 patients in the surge group and 10 among 39 patients in the hCG group (p . 054, Fisher exact test). Mean age and proportion of patients with male factor or tubal factor were not different. There were 15 patients who were dropped from the surge group and 8 from the hCG group, with failure to detect the LH surge being the most common reason. Conclusions: These data suggest a trend toward higher pregnancy rates with hCG to trigger ovulation for IUI. These findings could be partly due to a lower chance of cycle cancellation, but could also relate to oocyte maturation, corpus luteum function or endometrial readiness for implanta- tion. Clearly, the small sample size precludes justification for routine use of hCG given the higher cost. Subject accrual is continuing which may confirm or extend these data. Supported by: Medications provided by Serono Laboratories. P-113 Induction of ovulation and ovarian cancer: A meta-analysis. Sonya Kashyap, David Moher, Micheal Fung Kee Fung. Ctr for Reproductive Medicine, Weill Medical Coll, Cornell Univ, New York, NY; Univ of Ottawa, Ottawa, ON, Canada. Objective: To evaluate the current available data regarding induction of ovulation and the incidence of ovarian cancer. Design: Meta analysis Materials/Methods: A systematic review and meta analysis has been conducted. A comprehensive, literature search employing the following databases was done: Premedline, Medline, Cancerlit, Cinahl, Current con- tents and Biological abstracts. The search was not limited by language or year of publication. All citations were reviewed for relevance. The final group of citations was then reviewed for inclusion/exclusion criteria, quality assessment and data abstraction. This process has been completed by two independent reviewers. Discrepancies between reviewers have been re- solved by consensus. Citations were supplemented by references pulled from review articles and studies as well as hand searches (10 years) of 5 key journals. We also searched for grey/unpublished literature by consultation with content experts, reviews of conference proceedings, and we attempted contact with authors. Inclusion/Exclusion criteria included: outcome: pri- mary incident ovarian cancer of any histological type; population: women who had an explicit and reproducible diagnosis of infertility and these cases were to be compared with fertile and infertile controls; intervention/expo- sure: induction of ovulation by the following medications: clomiphene citrate, human menopausal gonadotropin, and gonadotropin releasing ago- nists. Data analyses was done using Revman 4.1 and Metaview 4.0. Cohort and case control data were analysed separately and infertile controls were used as the reference group where possible. Both fixed and random effects models were used for reasons identified in the manuscript Results: Original search revealed 2114 articles, which were reduced to 947 when limited to human, adult female. Relevance filter and manual removal of duplicates reduced the number further to 94. Inclusion/ exclu- sion criteria further reduced these numbers to 38. These also included : Search for unpublished literature revealed 2 studies whose results were at least partly published subsequently. Hand searching revealed 3 extra stud- ies. When multiple publication occurred only the most recent or complete papers were included. Precision of the search strategy was 1.6% and recall was 83%. In the final quantitative analysis 3 cohort studies and 7 case control studies were included. Case control data comparing infertile treated women with general population controls:OR 1.52 (1.16, 2.01); Case control data comparing infertile treated with infertile untreated: OR 1.00 (0.68, 1.46); Cohort data comparing infertile treated to infertile untreated : RR 0.66 (0.31, 1.41). Conclusions: These data do not support an increased risk of ovarian cancer as a result of induction of ovulation. In fact, fact the results are reassuring if not encouraging. There is a trend towards protection of infertile women from ovarian cancer via induction of ovulation. Supported by: None. P-114 Tissue sampling technique affects accuracy of karyotype from missed abortions. Ruth Bunker Lathi, Amin A. Milki. Stanford Univ Sch of Medicine, Stanford, CA. Objective: A high rate of 46XX results has been reported with cytoge- netic analysis of products of conception (POC) from first trimester missed abortions. This study evaluates whether a careful technique for villi selec- tion by the clinician, prior to specimen submission, will decrease false negative results caused by maternal contamination. Design: Retrospective review Materials/Methods: Since 1998, all patients with a missed abortion in the senior author’s (AAM) infertility practice were offered cytogenetic testing of the POC obtained by suction currettage. Prior to July 1999(group A n 15), POC were drained of blood then divided into a sample sent for histopathologic diagnosis and a sample for chromosomal testing. Since July 1999(group B n 40), the technique for choosing a sample for genetic analysis was changed in an attempt to improve diagnostic accuracy. The POC were drained of blood and rinsed in a saline basin then placed in a clean saline basin and carefully examined to identify chorionic villi. A sample of villi was dissected clear from other tissue using forceps and scissors then washed again and sent for chromosomal analysis. Cytogenetics reports from other physicians using the same lab during this time period were used for comparison (group C, n 59). Results: The percentage of 46XX results was significantly decreased in the test group when compared to historical and community controls: 30% vs 73% and 56% respectively. The percentage of aneuploid results was sig- nificantly higher in the test group: 60% vs 7% and 36% in the historical and community controls respectively. The mean ages were not significantly different. Study group Group A (n 15) Group B (n 40) Group C (n 59) Number 46XX (%)* 11 (73%) 12 (30%) 33 (56%) Number abnormal (%)** 1 (7%) 24 (60%) 21 (36%) Number 46XY 3 (20%) 4 (10%) 5 (8%) Mean Age 37.6 37.5 36.8 * B vs A p 0.005, B vs C p 0.014, B vs A Cp 0.004 ** B vs A p 0.0005, B vs C p 0.02, B vs A Cp 0.003 Conclusions: Although the cytogenetics laboratory personnel routinely attempts to isolate villus or fetal material from the submitted sample, a high proportion of 46XX results was seen in both groups where the technique described in this report was not applied. Thorough separation and cleaning of villi performed prior to sending missed abortion specimens allows S154 Abstracts Vol. 78, No. 3, Suppl. 1, September 2002

Clomiphene and intrauterine insemination (IUI)—what is the best way to time insemination?

Embed Size (px)

Citation preview

Page 1: Clomiphene and intrauterine insemination (IUI)—what is the best way to time insemination?

P-112

Clomiphene and intrauterine insemination (IUI)—What is the best wayto time insemination? Vivian Lewis, David S. Guzick. Univ of RochesterSch of Medicine and Dentistry, Rochester, NY.

Objective: Clomiphene citrate and IUI is frequently used to increasefecundity in couples with unexplained infertility. However, studies compar-ing methods of IUI timing are either retrospective or have inconsistentresults. We tested the hypothesis of whether pregnancy rates in womentreated with clomiphene and IUI would be different depending on whetherthe IUI was timed by spontaneous LH surge or hCG administration. Apositive pregnancy test with rising hCG concentrations was the main out-come measure.

Design: Prospective randomized clinical trialMaterials/Methods: Subjects were ovulatory women with at least one

patent tube and a partner or sperm donor with at least 4 million normalmotile sperm per ejaculate. Randomization was performed at the baselineultrasound, after which patients took 100 mg of clomiphene, days 5–9. Thesurge group began testing for LH surge using an over-the-counter kit on day12 and underwent IUI on the day after a positive test. Patients who failed todetect a surge were dropped from the study. The hCG group returned forultrasound starting on day 12 and received hCG when there was at least 1follicle measuring 20 mm mean diameter and when the endometrial thick-ness was at least 8 mm with a trilaminar pattern. If the LH kit becamepositive before ultrasound criteria were met, IUI was scheduled accordingly.Patients remained in the same study group in subsequent months for amaximum of 3 cycles. An intent to treat approach was used in analyzing thedata so that information from dropped cycles could be captured.

Results: Seventy-nine patients have completed 167 cycles with a total of19 pregnancies: 6/86 in the surge group and 13/81 in the hCG group (p �.075,chi-square). There were 4 viable pregnancies among 40 patients in thesurge group and 10 among 39 patients in the hCG group (p � . 054, Fisherexact test). Mean age and proportion of patients with male factor or tubalfactor were not different. There were 15 patients who were dropped from thesurge group and 8 from the hCG group, with failure to detect the LH surgebeing the most common reason.

Conclusions: These data suggest a trend toward higher pregnancy rateswith hCG to trigger ovulation for IUI. These findings could be partly due toa lower chance of cycle cancellation, but could also relate to oocytematuration, corpus luteum function or endometrial readiness for implanta-tion. Clearly, the small sample size precludes justification for routine use ofhCG given the higher cost. Subject accrual is continuing which may confirmor extend these data.

Supported by: Medications provided by Serono Laboratories.

P-113

Induction of ovulation and ovarian cancer: A meta-analysis. SonyaKashyap, David Moher, Micheal Fung Kee Fung. Ctr for ReproductiveMedicine, Weill Medical Coll, Cornell Univ, New York, NY; Univ ofOttawa, Ottawa, ON, Canada.

Objective: To evaluate the current available data regarding induction ofovulation and the incidence of ovarian cancer.

Design: Meta analysisMaterials/Methods: A systematic review and meta analysis has been

conducted. A comprehensive, literature search employing the followingdatabases was done: Premedline, Medline, Cancerlit, Cinahl, Current con-tents and Biological abstracts. The search was not limited by language oryear of publication. All citations were reviewed for relevance. The finalgroup of citations was then reviewed for inclusion/exclusion criteria, qualityassessment and data abstraction. This process has been completed by twoindependent reviewers. Discrepancies between reviewers have been re-solved by consensus. Citations were supplemented by references pulledfrom review articles and studies as well as hand searches (10 years) of 5 keyjournals. We also searched for grey/unpublished literature by consultationwith content experts, reviews of conference proceedings, and we attemptedcontact with authors. Inclusion/Exclusion criteria included: outcome: pri-mary incident ovarian cancer of any histological type; population: womenwho had an explicit and reproducible diagnosis of infertility and these caseswere to be compared with fertile and infertile controls; intervention/expo-sure: induction of ovulation by the following medications: clomiphenecitrate, human menopausal gonadotropin, and gonadotropin releasing ago-

nists. Data analyses was done using Revman 4.1 and Metaview 4.0. Cohortand case control data were analysed separately and infertile controls wereused as the reference group where possible. Both fixed and random effectsmodels were used for reasons identified in the manuscript

Results: Original search revealed 2114 articles, which were reduced to947 when limited to human, adult female. Relevance filter and manualremoval of duplicates reduced the number further to 94. Inclusion/ exclu-sion criteria further reduced these numbers to 38. These also included :Search for unpublished literature revealed 2 studies whose results were atleast partly published subsequently. Hand searching revealed 3 extra stud-ies. When multiple publication occurred only the most recent or completepapers were included. Precision of the search strategy was 1.6% and recallwas 83%. In the final quantitative analysis 3 cohort studies and 7 casecontrol studies were included. Case control data comparing infertile treatedwomen with general population controls:OR 1.52 (1.16, 2.01); Case controldata comparing infertile treated with infertile untreated: OR 1.00 (0.68,1.46); Cohort data comparing infertile treated to infertile untreated : RR0.66 (0.31, 1.41).

Conclusions: These data do not support an increased risk of ovariancancer as a result of induction of ovulation. In fact, fact the results arereassuring if not encouraging. There is a trend towards protection of infertilewomen from ovarian cancer via induction of ovulation.

Supported by: None.

P-114

Tissue sampling technique affects accuracy of karyotype from missedabortions. Ruth Bunker Lathi, Amin A. Milki. Stanford Univ Sch ofMedicine, Stanford, CA.

Objective: A high rate of 46XX results has been reported with cytoge-netic analysis of products of conception (POC) from first trimester missedabortions. This study evaluates whether a careful technique for villi selec-tion by the clinician, prior to specimen submission, will decrease falsenegative results caused by maternal contamination.

Design: Retrospective reviewMaterials/Methods: Since 1998, all patients with a missed abortion in the

senior author’s (AAM) infertility practice were offered cytogenetic testingof the POC obtained by suction currettage. Prior to July 1999(group A n �15), POC were drained of blood then divided into a sample sent forhistopathologic diagnosis and a sample for chromosomal testing. Since July1999(group B n � 40), the technique for choosing a sample for geneticanalysis was changed in an attempt to improve diagnostic accuracy. ThePOC were drained of blood and rinsed in a saline basin then placed in aclean saline basin and carefully examined to identify chorionic villi. Asample of villi was dissected clear from other tissue using forceps andscissors then washed again and sent for chromosomal analysis. Cytogeneticsreports from other physicians using the same lab during this time periodwere used for comparison (group C, n � 59).

Results: The percentage of 46XX results was significantly decreased inthe test group when compared to historical and community controls: 30% vs73% and 56% respectively. The percentage of aneuploid results was sig-nificantly higher in the test group: 60% vs 7% and 36% in the historical andcommunity controls respectively. The mean ages were not significantlydifferent.

Study group

Group A(n � 15)

Group B(n � 40)

Group C(n � 59)

Number 46XX (%)* 11 (73%) 12 (30%) 33 (56%)Number abnormal (%)** 1 (7%) 24 (60%) 21 (36%)Number 46XY 3 (20%) 4 (10%) 5 (8%)Mean Age 37.6 37.5 36.8

* B vs A p � 0.005, B vs C p � 0.014, B vs A � C p � 0.004** B vs A p � 0.0005, B vs C p � 0.02, B vs A � C p � 0.003

Conclusions: Although the cytogenetics laboratory personnel routinelyattempts to isolate villus or fetal material from the submitted sample, a highproportion of 46XX results was seen in both groups where the techniquedescribed in this report was not applied. Thorough separation and cleaningof villi performed prior to sending missed abortion specimens allows

S154 Abstracts Vol. 78, No. 3, Suppl. 1, September 2002