Professional Documents
Culture Documents
Advanced Fertility Center of Chicago Gurnee & Crystal Lake, Illinois Title of article: Relationship of follicle numbers and estradiol levels to multiple implantation in 3,608 intrauterine insemination cycles
Authors: Richard P. Dickey, Steven N. Taylor, Peter Y. Lu, Belinda M. Sartor, Phillip H. Rye, and Roman Pyrzak (from The Fertility Institute of New Orleans, New Orleans, Louisiana, USA, and the Section of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Louisiana State University School of Medicine) Source: Fertility and Sterility, January 2001 (Vol.75) Pages 69-78.
So how aggressive should we be we be with the ovarian stimulating drugs? How much do pregnancy rates differ according to how many follicles there are? What about effects on multiple pregnancy rates? Should we try to stimulate so that there are 2 eggs per month instead of the 1 that matures in a natural menstrual cycle? Or, should we try to get 3, or more than 3? Does the age of the woman matter much? Does the type of stimulating drug matter? Does the peak estrogen hormone level before ovulation matter?
There have been many studies done over the years that have investigated some of these important issues. Results have varied, and study sizes were often limited. This study looks at these issues again with a very large group of infertile couples.
3608 cycles were included in this analysis. All women were stimulated with either clomiphene or HMG, or both together in the same cycle. The fresh or frozen sperm had to be at least 30% motility and at least 10 million total sperm before processing, and at least 4 million total motile sperm after processing (to reduce the negative influence of severe male factor cases). Follicles and estradiol hormone levels were measured in the usual fashion of infertility clinics. Data was recorded in a computer database and analyzed with respect to number of follicles of various sizes (on the day of HCG), peak estradiol levels and outcomes of pregnancy, as well as single, twin, and triplet or higher order pregnancy.
Results: Clomiphene citrate cycles - Clomid Of 176 clomiphene pregnancies, 14 (8.0%) twin and three (1.7%) triplet or higher-order implantations. In clomiphene cycles, pregnancy was more closely related to the number of follicles > or = 15 mm than to follicles > or = 18 mm or those > or = 12 mm. Pregnancy was unrelated to estrogen (E2) level, E2 levels per follicle, or patient age. Learn more about Clomid treatment for unexplained infertility Learn more about Clomid treatment for ovulation problems and PCOS
For clomiphene cycles, pregnancy rates per cycle were constant from age < 28 to 41, and then declined dramatically (by 50%) from age 42 to 44. For HMG and clomiphene + HMG cycles, pregnancy rates were twice the rates for CC before age 32, but declined sharply thereafter, and were the same as the pregnancy rates for clomiphene after age 37. The incidence of multiple implantations in clomiphene pregnancies was 15% before age 30 and 8 to 10% after age 30. No triplet implantations occurred after age 33 in clomiphene cycles. The incidence of multiple implantations exceeded 20% before age 35 in HMG pregnancies and before age 39 in clomiphene + HMG pregnancies. No triplet or higher-order births occurred after age 34 in HMG and clomiphene + HMG patients.
In HMG cycles, the number of follicles decreased with age, from 7.3 before age 28 to 3.5 for ages 42 to 43. In clomiphene + HMG cycles, the number of follicles decreased from 5.8 before age 28 to 3.3 for ages 42 to 43. The implantation rates per follicle were identical for all three stimulation regimens and decreased sharply after age 39.
Follicle number
In HMG and clomiphene + HMG cycles for patients less than 35 years of age, the incidence of three or more implantations per cycle (but not of twin implantations) was tripled, while pregnancy rates were not significantly increased, when E2 was over 1000 pg/mL, when six or more follicles were > or = 12mm, and when four or more follicles were > or = 15mm.
In this study, pregnancy as well as triplet and higher-order implantations (but not twin implantations) were related to the number of follicles that were over 12 mm in clomiphene, HMG, and clomiphene + HMG cycles, and to E2 levels in HMG and clomiphene + HMG cycles. When values were below critical levels of six or more follicles >12mm, four or more follicles >15mm, and E2 levels >1000 in HMG and clomiphene + HMG cycles - and six or more follicles >12mm in CC cycles - triplet and higher-order implantations occurred in less than 1% of cycles and in less than 5% of pregnancies. When values were above these critical levels, triplet and higher-order implantations occurred in 2.8% to 3.2% of cycles and in 12% to 14% of pregnancies. The incidence of three or more implantations was identical in clomiphene and in HMG or clomiphene + HMG cycles when six or more follicles were >12mm. However, six or more follicles of >12mm occurred in only 5% of clomiphene cycles compared to 38% of HMG and 27% of clomiphene + HMG cycles. For patients age 35 and older, pregnancy rates in HMG and clomiphene + HMG cycles were doubled when six or more follicles were > or = 12mm without a significant increase in twin or higher order implantations. In clomiphene cycles, triple implantation occurred in 3.8% of cycles and 15.3% of pregnancies for patients less than 35 years old, when six or more follicles measured >12mm.
Conclusions:
Withholding HCG or IUI in clomiphene, HMG, and clomiphene + HMG cycles when six or more follicles are 12 mm or more in diameter may reduce triplet and higher-order implantations by 67% without significantly reducing pregnancy rates for patients under 35 years of age. For patients age 35 and older, withholding HCG under the same circumstances may decrease pregnancy rates by half without significantly reducing multiple implantations.