402
demanding of their caretakers. Questions about the past reproductive performance of donors are usually asked based upon the underlying assumption that pregnancy rates in the future are likely to correlate with previous successful ovarian hyperstimulation and embryo transfer. The recipients' own past experience, in many cases coupled with multiple consultations with respect to their own failed ART cycles, have educated these individuals and led to certain expectations. At times unrealistic expectations regarding donor performance arise from misinterpretations and extrapolations from previously gained information. Unfortunately the professional service rendered may, in such circumstances, be perceived as a de facto purchased commodity.
SUMMARY An older population of women is now increasingly seeking infertility care. The number of these patients may in fact eclipse those of younger patients for whom the method of oocyte donation was initially designed and previously offered. As a group, these older individuals appear to be energetic and demanding, with high expectations regarding the performance and the effectiveness of their fertility care. Physicians need to exercise vigilance in order to emphasize that eggs are not being bought and sold as a commodity and that guarantees of pregnancies cannot be made. Nevertheless, whereas oocyte donation requires all parties, donor, recipient, and doctor, to work together toward a common goal, it still offers women of advanced reproductive age perhaps their best chance at conception, pregnancy, and parenthood.
REFERENCES 1. Lutjen P, Trounson A, Leeton J, Findlay J, Wood C, Renou P: The establishment and maintenance of pregnancy using in vitro fertilization and embryo donation in a patient with primary ovarian failure. Nature 1984;307:174--175 2. Sauer MV, Paulson RJ: Human oocyte and preembryo donation: An evolving method for the treatment of infertility. Am J Obstet Gynecol 1990;163:1421-1424 3. Medical Research International; Society for Assisted Reproductive Technology, The American Fertility Society. In vitro fertilization-embryo transfer (IVF-ET) in the United States: 1990 results from the IVF-ET Registry. Fertil Steril 1992;57:15-24
SHORT COMMUNICATIONS
4. Saner MV, Paulson RJ, Lobo RA: A preliminary report on oocyte donation extending reproductive potential to women over 40. N Engl J Med 1990;323:1157-1160 5. Sauer MV, Paulson RJ, Macaso TM, Francis MM, Lobo RA: Establishment of a nonanonymous donor oocyte program: preliminary experience at the University of Southern California. Fertil Steril 1989;52:433-436
Mark V. Sauer 1 Richard J. Paulson Department of Obstetrics and Gynecology Division of Reproductive Endocrinology University of Southern California Los Angeles, California 90021 1 To whom correspondence should be addressed at Women's Hospital, 1240 North Mission Road, Room L946, Los Angeles, California 90033.
KIEL, GERMANY Pregnancies Following Transvaginal Gamete Intrafallopian Transfer (GIFT), Zygote Intrafallopian Transfer (ZIFT), and T u b a l E m b r y o - S t a g e T r a n s f e r ( T E S T ) in an in Vitro F e r t i l i z a t i o n ( I V F ) P r o g r a m
Submitted: March 11, 1992 Accepted: March 19, 1992
We report on the first pregnancies achieved at our clinic following transvaginal GIFT, ZIFT, and TEST. Our study population consisted of 15 patients in 17 treatment cycles. The mean age and duration of infertility were 32 and 5.4 years, respectively. The indications were male factor in eight cycles, unexplained infertility in seven cycles, and endometriosis in two cycles. Hormonal stimulation was performed with gonadotropin-releasing hormone analogue (Gn-RHa), human menopausal gonadotropin (hMG), and human chorionic gonadotropin (hCG) according to the protocol described by MacNamee et al. (1). Follicular aspiration and other laboratory maneuvers for semen preparation, insemination, and embryo culture were performed exactly as described previously (2). For the transvagJournal of Assisted Reproduction and Genetics, Vol. 9, No. 4, 1992
SHORT COMMUNICATIONS
403
Table I. Preliminary Results of Transvaginal G I F T / Z I F T and T E S T
Case
Age
C a u s e of infertility
Mode of E T a
No. of e m b r y o s transferred
Pregnancy
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
38 33 34 29 30 34 36 32 30 34 25 28 37 34 31 35 30
Endometriosis Male factor Male factor Unexplained Male factor Unexplained Male factor Male factor Unexplained Male factor Male factor Endometriosis Unexplained Unexplained Male factor Unexplained Unexplained
TEST TEST TEST TEST GIFT ZIFT TEST TEST TEST GIFT ZIFT TEST TEST TEST TEST TEST TEST
3 2 2 2 2b 2c 2 3 3 3b 3¢ 3 3 1 1 3 3
+ + + + -
a E m b r y o transfer. b Oocytes. c Zygotes.
inal replacement of gametes, zygotes, or embryos, a tubal catheter set (Labotect, G6ttingen, Germany) was used. Transvaginal GIFT was performed immediately after follicular aspiration using approximately 200,000 motile spermatozoa per transferred oocyte. Transvaginal ZIFT and TEST were performed 24 and 48 hr, respectively, after follicular aspiration. A maximum of three embryos, zygotes, or gametes was transferred to the tube without ultrasound guidance. No sedation or analgesia was required for this form of transfer and all patients could be released within 2 hr after the transfer. Up to now, we have achieved four pregnancies (Table I), two occurring in male factor, one in unexplained infertility, and the fourth in a patient with endometriosis. None of these pregnancies was tubal or ectopic. One women has delivered a healthy child, two pregnancies are ongoing, and one woman aborted during the seventh week of gestation. There is evidence from studies of rhesus monkeys that the transfer of embryos before compaction to the uterus is followed by a lower rate of pregnancy and a higher rate of abortion than when such embryos are transferred to the fallopian tube (3). Also, the results of Yovich et al. (4) showed convincingly that intratubal transfer techniques, GIFT, ZIFT, and TEST involve a substantially higher implantation rate. In 1987, Jansen and Anderson reported successful tubal catheterization from the vagina (5), and in 1988 JANSEN et al. reported the first pregnancy after transvaginal intraJournal o f Assisted Reproduction and Genetics, Vol. 9, No. 4, 1992
fallopian embryo transfer employing tubal cannulation by ultrasound guidance (6). In the following years, experience with these techniques has been improved (7). As regards pregnancy rate, our preliminary resuits suggest that transvaginal transfer of gametes, zygotes, or embryos may be a valuable method for the treatment of nontubal infertility which can improve the IVF success rate and promotes its acceptance. Our results show the following. (a) Direct transfer of gametes, zygotes, or embryos to the fallopian tube is possible without the need for anesthesia or ultrasound guidance. (b) The fallopian tube isthmus, around the time of ovulation, can be catheterized without later interference with ovum or embryo transfer to the uterus. Finally, and in order to reduce the risk of ectopic pregnancies, such techniques should be restricted to women with no previous history of pelvic inflammatory disease, ectopic pregnancy, or tubal surgery. REFERENCES 1. M a c N a m e e MC, Howles CM, E d w a r d s RG, Taylor PJ, Elder KT: Short-term luteinizing hormone-releasing h o r m o n e agonist treatment: Prospective trial of a novel ovarian stimulation for in vitro fertilization. Fertil Steril 1989;52:264-269 2. Mettler L, I n g e r m a n n Th: Aktueller Stand der Reproductionsmedizin. Gyn~ikologie 1989;2:117-123
404
SHORT COMMUNICATIONS
3. Marston JH, Penn R, Sivelle PC: Successful autotransfer of tubal eggs in the rhesus monkey. J Reprod Fertil 1977;49: 175-176 4. Yovich LJ, Yovich MJ, Edrisinghe RW: The relative chance of pregnancy following tubal or uterine procedures. Fertil Steril 1988;49:858-864 5. Jansen RPS, Anderson JC: Catheterization of the human fallopian tubes from the vagina. Lancet 1987;2:309-311 6. Jansen RPS, Anderson JC, Sutherland PD: Nonoperative embryo transfer to the fallopian tube. N Engl J Med 1988; 319:288-291 7. Bauer O, Van der Ven H, Diedrich K, A1-Hassani S, Krebs D, Gembruch U: Preliminary results on transvaginal tubal embryo stage transfer (TV-TEST) without ultrasound guidance. Hum Reprod 1990;5:553-556
T. A1-Hussaini L. Mettler1 M. Ibrahim S. Buck Department of Obstetrics and Gynecology University of Kiel Michaelisstra[3e 16 2300 Kiel, FRG 1 To whom correspondence should be addressed.
PARIS, FRANCE
Preliminary Data on the Efficacy of a New Human Menopausal Gonadotropin (hMG) Preparation Containing a Reduced Amount of Luteinizing Hormone (LH) for Superovulation in an in Vitro Fertilization (IVF) Program
Submitted: November 13, 1991 Accepted: April 15, 1992
INTRODUCTION The success of in vitro fertilization and embryo transfer (IVF/ET) is greatly enhanced by ovarian stimulation. The strategy of superovulation treatment is to recruit multiple mature follicles while creating a favorable hormonal environment that will allow implantation of at least one embryo.
Based on the two-cell theory of steroidogenesis, the synergistic action of both gonadotrophins is presumed necessary for follicular development. Moreover, it is well documented that, during the follicular phase, follicle stimulating hormone (FSH) is responsible for follicular recruitment, development, and selection, while only low amounts of luteinizing hormone (LH) are necessary for full steroidogenesis (1). The presence of high levels of L H during follicular development, on the other hand, seems to be detrimental to IVF/ET outcome (2). The present study was designed to assess the therapeutic efficacy and safety of a preparation of hMG containing a reduced amount of L H given during a long luteinizing hormone releasing hormone (LHRH) agonist protocol in normally ovulating women with tubal infertility who underwent IVF/ET.
MATERIALS AND METHODS A preparation of hMG containing 75 IU of FSH and 35 IU of LH (Pergogreen, Serono Laboratories, Boulogne, France) was used during a L H R H agonist IVF long protocol in 101 women less than 39 years old who had proven tubal infertility with no associated male factor. All were healthy individuals and gave written informed consent. After a minimum of 2 weeks of L H R H agonist (Triptorelin, 0.1 rag/day subcutaneously), which was started on day 2 of a menstrual cycle, Pergogreen was administered at a fixed dose of 3 ampoules/day i.m. for the first 6 days of treatment. Then the dose of Pergogreen was adjusted from 3 to a maximum of 6 ampoules per day according to the ovarian response. L H R H agonist treatment and gonadotropin support were continued until plasma levels of E 2 exceeded 500 pg/ml and at least two follicles t>15 mm were obtained. Ovulation was induced by a single injection of 10,000 IU human chorionic gonadotropin (hCG; Endo, Organon, SaintDenis, France) and surgical oocyte recovery was performed by transvaginal route 36 hr later. In all cases, the luteal phase was supported by local administration of progesterone (300 rag/day via the vaginal route) and/or intramuscular injection of hCG (2500 IU on days 1, 3, and 5 after pickup). This study was open and noncomparative. However, the results were compared with those obtained in our department with 90 patients who were selected by the same criteria and who were stimulated with an hMG preparation containing 75 IU of Journal of Assisted Reproduction and Genetics, Vol. 9, No. 4, 1992
demanding of their caretakers. Questions about the past reproductive performance of donors are usually asked based upon the underlying assumption that pregnancy rates in the future are likely to correlate with previous successful ovarian hyperstimulation and embryo transfer. The recipients' own past experience, in many cases coupled with multiple consultations with respect to their own failed ART cycles, have educated these individuals and led to certain expectations. At times unrealistic expectations regarding donor performance arise from misinterpretations and extrapolations from previously gained information. Unfortunately the professional service rendered may, in such circumstances, be perceived as a de facto purchased commodity.
SUMMARY An older population of women is now increasingly seeking infertility care. The number of these patients may in fact eclipse those of younger patients for whom the method of oocyte donation was initially designed and previously offered. As a group, these older individuals appear to be energetic and demanding, with high expectations regarding the performance and the effectiveness of their fertility care. Physicians need to exercise vigilance in order to emphasize that eggs are not being bought and sold as a commodity and that guarantees of pregnancies cannot be made. Nevertheless, whereas oocyte donation requires all parties, donor, recipient, and doctor, to work together toward a common goal, it still offers women of advanced reproductive age perhaps their best chance at conception, pregnancy, and parenthood.
REFERENCES 1. Lutjen P, Trounson A, Leeton J, Findlay J, Wood C, Renou P: The establishment and maintenance of pregnancy using in vitro fertilization and embryo donation in a patient with primary ovarian failure. Nature 1984;307:174--175 2. Sauer MV, Paulson RJ: Human oocyte and preembryo donation: An evolving method for the treatment of infertility. Am J Obstet Gynecol 1990;163:1421-1424 3. Medical Research International; Society for Assisted Reproductive Technology, The American Fertility Society. In vitro fertilization-embryo transfer (IVF-ET) in the United States: 1990 results from the IVF-ET Registry. Fertil Steril 1992;57:15-24
SHORT COMMUNICATIONS
4. Saner MV, Paulson RJ, Lobo RA: A preliminary report on oocyte donation extending reproductive potential to women over 40. N Engl J Med 1990;323:1157-1160 5. Sauer MV, Paulson RJ, Macaso TM, Francis MM, Lobo RA: Establishment of a nonanonymous donor oocyte program: preliminary experience at the University of Southern California. Fertil Steril 1989;52:433-436
Mark V. Sauer 1 Richard J. Paulson Department of Obstetrics and Gynecology Division of Reproductive Endocrinology University of Southern California Los Angeles, California 90021 1 To whom correspondence should be addressed at Women's Hospital, 1240 North Mission Road, Room L946, Los Angeles, California 90033.
KIEL, GERMANY Pregnancies Following Transvaginal Gamete Intrafallopian Transfer (GIFT), Zygote Intrafallopian Transfer (ZIFT), and T u b a l E m b r y o - S t a g e T r a n s f e r ( T E S T ) in an in Vitro F e r t i l i z a t i o n ( I V F ) P r o g r a m
Submitted: March 11, 1992 Accepted: March 19, 1992
We report on the first pregnancies achieved at our clinic following transvaginal GIFT, ZIFT, and TEST. Our study population consisted of 15 patients in 17 treatment cycles. The mean age and duration of infertility were 32 and 5.4 years, respectively. The indications were male factor in eight cycles, unexplained infertility in seven cycles, and endometriosis in two cycles. Hormonal stimulation was performed with gonadotropin-releasing hormone analogue (Gn-RHa), human menopausal gonadotropin (hMG), and human chorionic gonadotropin (hCG) according to the protocol described by MacNamee et al. (1). Follicular aspiration and other laboratory maneuvers for semen preparation, insemination, and embryo culture were performed exactly as described previously (2). For the transvagJournal of Assisted Reproduction and Genetics, Vol. 9, No. 4, 1992
SHORT COMMUNICATIONS
403
Table I. Preliminary Results of Transvaginal G I F T / Z I F T and T E S T
Case
Age
C a u s e of infertility
Mode of E T a
No. of e m b r y o s transferred
Pregnancy
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
38 33 34 29 30 34 36 32 30 34 25 28 37 34 31 35 30
Endometriosis Male factor Male factor Unexplained Male factor Unexplained Male factor Male factor Unexplained Male factor Male factor Endometriosis Unexplained Unexplained Male factor Unexplained Unexplained
TEST TEST TEST TEST GIFT ZIFT TEST TEST TEST GIFT ZIFT TEST TEST TEST TEST TEST TEST
3 2 2 2 2b 2c 2 3 3 3b 3¢ 3 3 1 1 3 3
+ + + + -
a E m b r y o transfer. b Oocytes. c Zygotes.
inal replacement of gametes, zygotes, or embryos, a tubal catheter set (Labotect, G6ttingen, Germany) was used. Transvaginal GIFT was performed immediately after follicular aspiration using approximately 200,000 motile spermatozoa per transferred oocyte. Transvaginal ZIFT and TEST were performed 24 and 48 hr, respectively, after follicular aspiration. A maximum of three embryos, zygotes, or gametes was transferred to the tube without ultrasound guidance. No sedation or analgesia was required for this form of transfer and all patients could be released within 2 hr after the transfer. Up to now, we have achieved four pregnancies (Table I), two occurring in male factor, one in unexplained infertility, and the fourth in a patient with endometriosis. None of these pregnancies was tubal or ectopic. One women has delivered a healthy child, two pregnancies are ongoing, and one woman aborted during the seventh week of gestation. There is evidence from studies of rhesus monkeys that the transfer of embryos before compaction to the uterus is followed by a lower rate of pregnancy and a higher rate of abortion than when such embryos are transferred to the fallopian tube (3). Also, the results of Yovich et al. (4) showed convincingly that intratubal transfer techniques, GIFT, ZIFT, and TEST involve a substantially higher implantation rate. In 1987, Jansen and Anderson reported successful tubal catheterization from the vagina (5), and in 1988 JANSEN et al. reported the first pregnancy after transvaginal intraJournal o f Assisted Reproduction and Genetics, Vol. 9, No. 4, 1992
fallopian embryo transfer employing tubal cannulation by ultrasound guidance (6). In the following years, experience with these techniques has been improved (7). As regards pregnancy rate, our preliminary resuits suggest that transvaginal transfer of gametes, zygotes, or embryos may be a valuable method for the treatment of nontubal infertility which can improve the IVF success rate and promotes its acceptance. Our results show the following. (a) Direct transfer of gametes, zygotes, or embryos to the fallopian tube is possible without the need for anesthesia or ultrasound guidance. (b) The fallopian tube isthmus, around the time of ovulation, can be catheterized without later interference with ovum or embryo transfer to the uterus. Finally, and in order to reduce the risk of ectopic pregnancies, such techniques should be restricted to women with no previous history of pelvic inflammatory disease, ectopic pregnancy, or tubal surgery. REFERENCES 1. M a c N a m e e MC, Howles CM, E d w a r d s RG, Taylor PJ, Elder KT: Short-term luteinizing hormone-releasing h o r m o n e agonist treatment: Prospective trial of a novel ovarian stimulation for in vitro fertilization. Fertil Steril 1989;52:264-269 2. Mettler L, I n g e r m a n n Th: Aktueller Stand der Reproductionsmedizin. Gyn~ikologie 1989;2:117-123
404
SHORT COMMUNICATIONS
3. Marston JH, Penn R, Sivelle PC: Successful autotransfer of tubal eggs in the rhesus monkey. J Reprod Fertil 1977;49: 175-176 4. Yovich LJ, Yovich MJ, Edrisinghe RW: The relative chance of pregnancy following tubal or uterine procedures. Fertil Steril 1988;49:858-864 5. Jansen RPS, Anderson JC: Catheterization of the human fallopian tubes from the vagina. Lancet 1987;2:309-311 6. Jansen RPS, Anderson JC, Sutherland PD: Nonoperative embryo transfer to the fallopian tube. N Engl J Med 1988; 319:288-291 7. Bauer O, Van der Ven H, Diedrich K, A1-Hassani S, Krebs D, Gembruch U: Preliminary results on transvaginal tubal embryo stage transfer (TV-TEST) without ultrasound guidance. Hum Reprod 1990;5:553-556
T. A1-Hussaini L. Mettler1 M. Ibrahim S. Buck Department of Obstetrics and Gynecology University of Kiel Michaelisstra[3e 16 2300 Kiel, FRG 1 To whom correspondence should be addressed.
PARIS, FRANCE
Preliminary Data on the Efficacy of a New Human Menopausal Gonadotropin (hMG) Preparation Containing a Reduced Amount of Luteinizing Hormone (LH) for Superovulation in an in Vitro Fertilization (IVF) Program
Submitted: November 13, 1991 Accepted: April 15, 1992
INTRODUCTION The success of in vitro fertilization and embryo transfer (IVF/ET) is greatly enhanced by ovarian stimulation. The strategy of superovulation treatment is to recruit multiple mature follicles while creating a favorable hormonal environment that will allow implantation of at least one embryo.
Based on the two-cell theory of steroidogenesis, the synergistic action of both gonadotrophins is presumed necessary for follicular development. Moreover, it is well documented that, during the follicular phase, follicle stimulating hormone (FSH) is responsible for follicular recruitment, development, and selection, while only low amounts of luteinizing hormone (LH) are necessary for full steroidogenesis (1). The presence of high levels of L H during follicular development, on the other hand, seems to be detrimental to IVF/ET outcome (2). The present study was designed to assess the therapeutic efficacy and safety of a preparation of hMG containing a reduced amount of L H given during a long luteinizing hormone releasing hormone (LHRH) agonist protocol in normally ovulating women with tubal infertility who underwent IVF/ET.
MATERIALS AND METHODS A preparation of hMG containing 75 IU of FSH and 35 IU of LH (Pergogreen, Serono Laboratories, Boulogne, France) was used during a L H R H agonist IVF long protocol in 101 women less than 39 years old who had proven tubal infertility with no associated male factor. All were healthy individuals and gave written informed consent. After a minimum of 2 weeks of L H R H agonist (Triptorelin, 0.1 rag/day subcutaneously), which was started on day 2 of a menstrual cycle, Pergogreen was administered at a fixed dose of 3 ampoules/day i.m. for the first 6 days of treatment. Then the dose of Pergogreen was adjusted from 3 to a maximum of 6 ampoules per day according to the ovarian response. L H R H agonist treatment and gonadotropin support were continued until plasma levels of E 2 exceeded 500 pg/ml and at least two follicles t>15 mm were obtained. Ovulation was induced by a single injection of 10,000 IU human chorionic gonadotropin (hCG; Endo, Organon, SaintDenis, France) and surgical oocyte recovery was performed by transvaginal route 36 hr later. In all cases, the luteal phase was supported by local administration of progesterone (300 rag/day via the vaginal route) and/or intramuscular injection of hCG (2500 IU on days 1, 3, and 5 after pickup). This study was open and noncomparative. However, the results were compared with those obtained in our department with 90 patients who were selected by the same criteria and who were stimulated with an hMG preparation containing 75 IU of Journal of Assisted Reproduction and Genetics, Vol. 9, No. 4, 1992
