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Selective oocyte retrieval: a new approach to ovarian hyperstimulation
FERTILITY AND STERILITY
Vol. 50, No. 4, October 1988
Copyright 0 1988 The American Fertility Society
Printed in U.S.A .
Selective oocyte retrieval: a new approach to ovarian hyperstimulation Joelle Belaisch-Allart, M.D.*t Jean Belaisch, M.D.:j: Andre Hazout, M.D.*
Jacques Testart, Ph.D.§ Rene Frydman, M.D.*
Hopital Antoine Beclere, Unite 187 Institut National de la Sante et de la Recherche Medicale, Clamart, and Hopital Saint Vincent de Paul, Paris, France
Usual therapies of ovarian hyperstimulation (OHS) are limited to treatment of its consequences. When a multiple pregnancy is detected, embryo reduction, also called selective abortion, 1 is one possible solution, but this only avoids multiple pregnancy. It does not eliminate other side effects that arise at earlier stages of OHS. It is now possible to monitor ovulation through rapid plasma estradiol (E 2 ) assays and follicle ultrasonography. Severe hyperstimulation should therefore no longer occur during human menopausal gonadotropin (hMG) or pure follicle-stimulating hormone (FSH) treatment. However, when stimulations similar to those used in in vitro fertilization (IVF) are not followed by oocyte retrieval or are carried out in women with polycystic ovaries due to gonadotropin sensitivity, hyperstimulation can arise. A series of complications has been described under the general term of OHS. The ovarian response is classified in three main clinical categories: mild, moderate, and severe hyperstimulation, according to clinical symptoms signs and laboratory findings. 2 OHS is often associated with high preovulatory E 2 levels. 2 Previously, the prevention of OHS was suppresReceived January 11, 1988; revised and accepted June 16, 1988. *Service de Gynecologie-Obstetrique, (Prof. E. Papiernik), Hopi tal Antoine Beclere. t Reprint requests: J. Belaisch-Allart, M.D., Service de Gynecologie-Obstetrique, Hopital A. Beclere, 92141 Clamart, France. t Service de Gynecologie-Obstetrique, Hopital Saint Vincent de Paul. §Unite INSERM 187, Hopital A. Beclere.
654
Belaisch-Allart et al.
Communication-in-brief
sion of the human chorionic gonadotropin (hCG) injection. The patient was also advised not to have sexual intercourse. This treatment did not entirely eliminate the risk of hyperstimulation. Hence, the idea of follicular reduction or selective ovocyte retrieval was introduced. Initially, we suggested a technique called follicle reduction, which consists of treating OHS by puncturing the majority of the follicles on the 11th or 12th day of the cycle and leaving one or two intact. 3 However, observations made during laparoscopic oocyte retrieval attempt for IVF led us to review this reduction technique. In the absence of luteinizing hormone (LH) discharge or hCG administration, the cumulus cells were not dissociated and the oocyte was not loosened during the aspiration of the follicle content. Furthermore, the punctured follicles were filled with blood and expanded. We therefore asked ourselves what could happen to the oocytes that were left after a simple follicle reduction and whether there was a risk of spontaneous LH discharge, which could lead to the subsequent follicle rupture, releasing the mature oocyte. These considerations led to our developing a new technique that consists in selective oocyte retrieval followed by embryo freezing.
CASE REPORTS
We performed the technique of selective oocyte retrieval on three patients who were referred to our hospital after developing severe multiple follicular maturation. They had received hMG or pure FSH for polycystic ovarie~ in cases 1 and 3 and for ovula-
Fertility and Sterility
Table 1
a
Clinical Features of the Three Patients Who Were Submited to Selective Oocyte Retrieval
Patients
Ovulation stimulation
E2 (pg/ml) at hCG injection
Punctured follicles
Retrieved oocytes
Frozen embryos
1" 2" 3
FSH hMG FSH
3750 2130 2475
10
6 3 2
4 2 1
7 20
Ongoing pregnancy after selective oocyte retrieval.
tion disorders in case 2 (Table 1). Although hCG administration is usually contraindicated in this case, 2 hCG was injected as soon as the follicles had reached the maturity required for IVF. The patients were told to have sexual intercourse the day after hCG injection. Ultrasonically guided oocyte retrieval took place 35 ± 1 hours after hCG injection as in our IVF program. 4 All but one follicle were removed from each ovary. The retrieved follicles were given to the IVF laboratory, and the oocytes thus obtained were fertilized with the· husband's semen. All embryos obtained in this manner were frozen. 5 RESULTS
Of the three patients, two had successful pregnancies after oocyte retrieval and have given birth to normal singleton; moreover, they have frozen embryos in our laboratory. The third patient suffered from a severe polycystic ovarian disease and has received hMG or pure FSH without success for more than 1 year in an attempt to obtain an ovulation for the transfer of the frozen embryo. In this small series, no complications occurred. We did, however, note a low ratio of oocytes per follicles (11 out of 37, i.e., 29.7%, see Table 1). The cleavage rate was in the usual range (7 out of 11, i.e., 63%, see Table 1) comparable to the usual results of our IVF units with clomiphene-hMG ovarian stimulation. 4 DISCUSSION
This technique is attractive. We are sure that the recovered oocytes are removed from the follicles, and we also avoid wasting the excessive oocyte production in patients who respond exceptionally well to stimulation. We do, however, have certain reservations: the patients experienced some pelvic pain in the days after oocyte retrieval. Our experience in IVF has shown that the E 2 level is high in the
Vol. 50, No.4, October 1988
luteal phase despite oocyte retrieval. 6 However, the IVF teams who have experienced cases of OHS used several hCG injections during the luteal phase. In Clamart after more than 1500 IVF attempts, none of our patients has been rehospitalized for hyperstimulation except after use of luteinizing hormone-releasing hormone (LH-RH) agonist. Selective oocyte retrieval can be used only when embryo freezing is possible. It is a rather costly procedure for the patient in countries where the IVF procedure is not free. Selective oocyte retrieval may appear to be a traumatic procedure to the patients, and it should be proposed only to patients who have had previously stimulation cycles stopped for OHS. This method might encourage gynecologists to induce voluntary hyperstimulations in order to carry out IVF. This is not our aim. We simply wish to preserve the possibility of pregnancy in cases where the patient has responded exceptionally well to a controlled ovulation stimulation. In conclusion, selective oocyte retrieval is one possible approach to multiple follicular development. It avoids canceling the cycle, but the technique should only be used in exceptional cases: it cannot replace proper monitoring of ovarian stimulation through plasma E 2 assays and sonography.
SUMMARY
Selective oocyte retrieval is a new approach to ovarian hyperstimulation (OHS) that prevents side effects of OHS and multiple pregnancies by puncturing most of the ovarian follicles 35 hours after hCG administration as in an IVF program. The remaining intact follicles can still result in a singleton or twin pregnancy. In three patients who presented a multiple follicular development, this technique resulted in two pregnancies; moreover, the retrieved oocytes were fertilized and the embryos frozen.
Belaisch-Allart et al.
Communication-in-brief
655
REFERENCES 1. Bessis R: Interruption selective de grossesse. Horm Reprod
Metab 4:85, 1987 2. Schenker G, Weinstein D: Ovarian hyperstimulation syndrome: a current survey. Fertil Steril30:255, 1978 3. Hazout A, Porchier J, Frydman R: Une alternative ala reduction embryonnaire: la reduction folliculaire. Gynecologie 35:119, 1984 4. Belaisch-Allart J, Hazout A, Guillet-Rosso F, Glissant M,
656
Belaisch-Allart et al.
Communication-in-brief
Testart J, Frydman R: Various techniques for oocyte recovery in an in vitro fertilization and embryo transfer program. J In Vitro Fert Embryo Transfer 2:99, 1985 5. Testart J, Lassalle B, Belaisch-Allart J, Hazout A, Forman R, Rainhorn JD, Frydman R: High pregnancy rate after early human embryo freezing. Fertil Steril46:268, 1986 6. Belaisch-AHart J, Testart J, Fries N, Forman RG, Frydman R: The effect of dydrogesterone supplementation in an IVF programme. Hum Reprod 2:183, 1987
Fertility and Sterility
Vol. 50, No. 4, October 1988
Copyright 0 1988 The American Fertility Society
Printed in U.S.A .
Selective oocyte retrieval: a new approach to ovarian hyperstimulation Joelle Belaisch-Allart, M.D.*t Jean Belaisch, M.D.:j: Andre Hazout, M.D.*
Jacques Testart, Ph.D.§ Rene Frydman, M.D.*
Hopital Antoine Beclere, Unite 187 Institut National de la Sante et de la Recherche Medicale, Clamart, and Hopital Saint Vincent de Paul, Paris, France
Usual therapies of ovarian hyperstimulation (OHS) are limited to treatment of its consequences. When a multiple pregnancy is detected, embryo reduction, also called selective abortion, 1 is one possible solution, but this only avoids multiple pregnancy. It does not eliminate other side effects that arise at earlier stages of OHS. It is now possible to monitor ovulation through rapid plasma estradiol (E 2 ) assays and follicle ultrasonography. Severe hyperstimulation should therefore no longer occur during human menopausal gonadotropin (hMG) or pure follicle-stimulating hormone (FSH) treatment. However, when stimulations similar to those used in in vitro fertilization (IVF) are not followed by oocyte retrieval or are carried out in women with polycystic ovaries due to gonadotropin sensitivity, hyperstimulation can arise. A series of complications has been described under the general term of OHS. The ovarian response is classified in three main clinical categories: mild, moderate, and severe hyperstimulation, according to clinical symptoms signs and laboratory findings. 2 OHS is often associated with high preovulatory E 2 levels. 2 Previously, the prevention of OHS was suppresReceived January 11, 1988; revised and accepted June 16, 1988. *Service de Gynecologie-Obstetrique, (Prof. E. Papiernik), Hopi tal Antoine Beclere. t Reprint requests: J. Belaisch-Allart, M.D., Service de Gynecologie-Obstetrique, Hopital A. Beclere, 92141 Clamart, France. t Service de Gynecologie-Obstetrique, Hopital Saint Vincent de Paul. §Unite INSERM 187, Hopital A. Beclere.
654
Belaisch-Allart et al.
Communication-in-brief
sion of the human chorionic gonadotropin (hCG) injection. The patient was also advised not to have sexual intercourse. This treatment did not entirely eliminate the risk of hyperstimulation. Hence, the idea of follicular reduction or selective ovocyte retrieval was introduced. Initially, we suggested a technique called follicle reduction, which consists of treating OHS by puncturing the majority of the follicles on the 11th or 12th day of the cycle and leaving one or two intact. 3 However, observations made during laparoscopic oocyte retrieval attempt for IVF led us to review this reduction technique. In the absence of luteinizing hormone (LH) discharge or hCG administration, the cumulus cells were not dissociated and the oocyte was not loosened during the aspiration of the follicle content. Furthermore, the punctured follicles were filled with blood and expanded. We therefore asked ourselves what could happen to the oocytes that were left after a simple follicle reduction and whether there was a risk of spontaneous LH discharge, which could lead to the subsequent follicle rupture, releasing the mature oocyte. These considerations led to our developing a new technique that consists in selective oocyte retrieval followed by embryo freezing.
CASE REPORTS
We performed the technique of selective oocyte retrieval on three patients who were referred to our hospital after developing severe multiple follicular maturation. They had received hMG or pure FSH for polycystic ovarie~ in cases 1 and 3 and for ovula-
Fertility and Sterility
Table 1
a
Clinical Features of the Three Patients Who Were Submited to Selective Oocyte Retrieval
Patients
Ovulation stimulation
E2 (pg/ml) at hCG injection
Punctured follicles
Retrieved oocytes
Frozen embryos
1" 2" 3
FSH hMG FSH
3750 2130 2475
10
6 3 2
4 2 1
7 20
Ongoing pregnancy after selective oocyte retrieval.
tion disorders in case 2 (Table 1). Although hCG administration is usually contraindicated in this case, 2 hCG was injected as soon as the follicles had reached the maturity required for IVF. The patients were told to have sexual intercourse the day after hCG injection. Ultrasonically guided oocyte retrieval took place 35 ± 1 hours after hCG injection as in our IVF program. 4 All but one follicle were removed from each ovary. The retrieved follicles were given to the IVF laboratory, and the oocytes thus obtained were fertilized with the· husband's semen. All embryos obtained in this manner were frozen. 5 RESULTS
Of the three patients, two had successful pregnancies after oocyte retrieval and have given birth to normal singleton; moreover, they have frozen embryos in our laboratory. The third patient suffered from a severe polycystic ovarian disease and has received hMG or pure FSH without success for more than 1 year in an attempt to obtain an ovulation for the transfer of the frozen embryo. In this small series, no complications occurred. We did, however, note a low ratio of oocytes per follicles (11 out of 37, i.e., 29.7%, see Table 1). The cleavage rate was in the usual range (7 out of 11, i.e., 63%, see Table 1) comparable to the usual results of our IVF units with clomiphene-hMG ovarian stimulation. 4 DISCUSSION
This technique is attractive. We are sure that the recovered oocytes are removed from the follicles, and we also avoid wasting the excessive oocyte production in patients who respond exceptionally well to stimulation. We do, however, have certain reservations: the patients experienced some pelvic pain in the days after oocyte retrieval. Our experience in IVF has shown that the E 2 level is high in the
Vol. 50, No.4, October 1988
luteal phase despite oocyte retrieval. 6 However, the IVF teams who have experienced cases of OHS used several hCG injections during the luteal phase. In Clamart after more than 1500 IVF attempts, none of our patients has been rehospitalized for hyperstimulation except after use of luteinizing hormone-releasing hormone (LH-RH) agonist. Selective oocyte retrieval can be used only when embryo freezing is possible. It is a rather costly procedure for the patient in countries where the IVF procedure is not free. Selective oocyte retrieval may appear to be a traumatic procedure to the patients, and it should be proposed only to patients who have had previously stimulation cycles stopped for OHS. This method might encourage gynecologists to induce voluntary hyperstimulations in order to carry out IVF. This is not our aim. We simply wish to preserve the possibility of pregnancy in cases where the patient has responded exceptionally well to a controlled ovulation stimulation. In conclusion, selective oocyte retrieval is one possible approach to multiple follicular development. It avoids canceling the cycle, but the technique should only be used in exceptional cases: it cannot replace proper monitoring of ovarian stimulation through plasma E 2 assays and sonography.
SUMMARY
Selective oocyte retrieval is a new approach to ovarian hyperstimulation (OHS) that prevents side effects of OHS and multiple pregnancies by puncturing most of the ovarian follicles 35 hours after hCG administration as in an IVF program. The remaining intact follicles can still result in a singleton or twin pregnancy. In three patients who presented a multiple follicular development, this technique resulted in two pregnancies; moreover, the retrieved oocytes were fertilized and the embryos frozen.
Belaisch-Allart et al.
Communication-in-brief
655
REFERENCES 1. Bessis R: Interruption selective de grossesse. Horm Reprod
Metab 4:85, 1987 2. Schenker G, Weinstein D: Ovarian hyperstimulation syndrome: a current survey. Fertil Steril30:255, 1978 3. Hazout A, Porchier J, Frydman R: Une alternative ala reduction embryonnaire: la reduction folliculaire. Gynecologie 35:119, 1984 4. Belaisch-Allart J, Hazout A, Guillet-Rosso F, Glissant M,
656
Belaisch-Allart et al.
Communication-in-brief
Testart J, Frydman R: Various techniques for oocyte recovery in an in vitro fertilization and embryo transfer program. J In Vitro Fert Embryo Transfer 2:99, 1985 5. Testart J, Lassalle B, Belaisch-Allart J, Hazout A, Forman R, Rainhorn JD, Frydman R: High pregnancy rate after early human embryo freezing. Fertil Steril46:268, 1986 6. Belaisch-AHart J, Testart J, Fries N, Forman RG, Frydman R: The effect of dydrogesterone supplementation in an IVF programme. Hum Reprod 2:183, 1987
Fertility and Sterility