We have reviewed the pregnancy rate and outcome of 25 patients who underwent tubocornual anastomo... more We have reviewed the pregnancy rate and outcome of 25 patients who underwent tubocornual anastomosis for correction of proximal tubal occlusion at Yale-New Haven Hospital between 1977 and 1981. Tubal occlusion was the result of previous tubal sterilization in 17 patients (11 laparoscopic electrocautery and 6 tubal ligation) and previous tubal infection in 8. Fourteen of the patients conceived (56%). Viable pregnancy was achieved in nine patients (36%) and tubal pregnancy in three (12%). No significant difference in pregnancy rates was found between patients with diseased cornua and those previously sterilized by either electrocautery or tubal ligation. Tubal length of greater than or equal to 4 cm following corrective surgery as compared with less than or equal to 4 cm did not influence pregnancy rates. The patients with the shorter oviducts had a higher rate of early pregnancy wastage. All three tubal pregnancies occurred in patients with reoccluded fallopian tubes as demonstrated by a hysterosalpingogram. We conclude that tubocornual anastomosis still remains the treatment of choice for patients with proximal tubal obstruction.
This study compares the in vitro fertilization and cleavage rates of paired first- and last-recov... more This study compares the in vitro fertilization and cleavage rates of paired first- and last-recovered preovulatory human oocytes that were exposed to a 100% CO2 pneumoperitoneum and general anesthesia. In 305 consecutive cycles of laparoscopy, 1741 oocytes (5.7/cycle) were recovered. The exact time of aspiration (T) was recorded for each oocyte. The time interval (T1 to T2) between recovery of first and last oocytes ranged from 0 to 38 minutes and represented differences in the exposure time of first and last oocytes to the CO2 pneumoperitoneum and to general anesthesia. For all cycles (n = 305) without regard for T1 to T2, last-recovered oocytes fertilized less often than first-recovered eggs (P = 0.06; McNemar's test). When T1 to T2 was short (less than or equal to 5 minutes), first- and last-recovered oocytes fertilized at comparable rates (70.8% and 74.0%). When only cycles with T1 to T2 greater than 5 minutes were considered (n = 209), the difference in fertilization rates ...
The utility of magnetic resonance (MR) imaging in assessing response to therapy with a gonadotrop... more The utility of magnetic resonance (MR) imaging in assessing response to therapy with a gonadotropin-releasing hormone (GnRH) analog was assessed in 19 women with uterine leiomyomas and 19 women with endometriosis. There was a significant reduction in individual fibroid volumes at 3 months (P less than .05) and at 6 months (P less than .005) in the drug group, whereas there was no significant change in the placebo group. Vessel conspicuity significantly decreased at 3 months (P less than .02) and at 6 months (P less than .01) in the drug group but not in the placebo group. In the patients with endometriosis, there was a significant decrease (P less than .0006) in the number of endometriomas visualized. Significant changes were also noted in the pelvis in women who were receiving the GnRH analog. After 6 months of therapy, the identifiability of the ovaries was significantly poorer (P less than .05). The authors conclude that the utility of conservative therapy with a GnRH analog can be quantitatively assessed with MR imaging.
The performance of in vitro fertilization-embryo transfer (IVF-ET) programs is summarized typical... more The performance of in vitro fertilization-embryo transfer (IVF-ET) programs is summarized typically as the average probability of achieving pregnancy per cycle. Variation in conception probabilities across women reduces the usefulness of such an aggregate measure. More relevant is the conditional probability of achieving pregnancy on a given cycle following a number of failed IVF-ET attempts. We construct a model that accurately describes 1,257 treatment cycles performed at Yale over 571 different women. The model assumes a split population, where some women can never conceive via IVF-ET, while the remaining women have identical and constant per cycle probabilities of conception. This model produces estimates that are highly consistent with the data, and suggests that continuing treatment beyond some threshold number of cycles is not efficacious. Recognizing this, we determine cutoffs beyond which treatment should not continue for IVF-ET programs with fixed capacities. We also consider cutoff policies where program participants may belong to one of several different split populations, detailing the case of two groups. Finally, we show how one may reduce the average time in treatment (including waiting time) considerably with minimal impact on the probability of achieving pregnancy.
In contradistinction to other biological systems, the reproductive mechanisms in sexually reprodu... more In contradistinction to other biological systems, the reproductive mechanisms in sexually reproducing species are unique in that their success relies upon a synchronous interaction between two separate individuals. Reproduction has become increasingly more efficient as higher forms have developed internal fertilization and gestation. Although our anthropomorphic perspective has dominated the understanding of reproductive processes, 'recent discoveries' make it clear that this reproductive efficiency has been gained by retention of previously present biological mechanisms whose origins are in the vestigial excretory tracts and ducts which are the precursors of the reproductive tract. We refer to these as 'archetypal systems'. They include the interaction between sex steroid sensitive tissues and sex steroids, the renin-angiotensin system and the macrophage/monokine response to infection. Through these mechanisms the reproductive tracts have maintained control over the microenvironment in which the reproductive processes occur. Thus, gamete development in male and female, and fertilization and early embryonic existence in the female tract prior to implantation still occur in compartments which are extracorporeal, i.e., separated from blood or subendothelial spaces, and are controlled by cellular mechanisms found in ancient excretory tracts. Since the majority of the changes between lower forms and contemporary mammals are anatomical modifications which have favoured the success of these extracorporeal events within the developing, generally land-based mammals, we should take special note of lower animals, understanding the evolutionary appropriation of mechanisms designed to furnish the suitable microenvironment from the surrounding tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
To determine if the timing of the onset of pituitary desensitization and ovarian suppression usin... more To determine if the timing of the onset of pituitary desensitization and ovarian suppression using follicular phase leuprolide acetate (LA) is associated with in vitro fertilization-embryo transfer (IVF-ET) success for pregnancy. Retrospective series of IVF patients undergoing pituitary desensitization and ovarian suppression before beginning controlled ovarian hyperstimulation for IVF-ET. Tertiary infertility practice. Seventy-eight women for 80 cycles began LA on day 1 of their menstrual cycle. After 11 days of LA, 47 (59%) cycles in group I had suppressed serum estradiol (E2) levels less than 40 pg/mL, in contrast to 33 (41%) cycles in group II not adequately suppressed, thereby requiring additional days to achieve suppression. Controlled ovarian hyperstimulation was started when patients were satisfactorily suppressed, i.e., E2 less than 40 pg/mL. Mean E2 response, ampules of human menopausal gonadotropin, cancellation rates, number of oocytes retrieved, fertilization rates, and...
Twenty-one patients with intractable uterine bleeding were treated by resectoscopic ablation of t... more Twenty-one patients with intractable uterine bleeding were treated by resectoscopic ablation of the endometrium. All the patients were worked up thoroughly to rule out hormonal or anatomic reasons for their bleeding. In addition, various hormonal regimens were tried to stop the bleeding. Our technique used the modified urologic resectoscope, which is inserted into the uterine cavity. The entire endometrial cavity was ablated using 30 W of coagulating current. Of the 21 patients treated, 14 had blood dyscrasias, four were poor anesthetic risks, and three refused hysterectomy. There were no complications from the procedure. Three patients died from their primary disease, and all the rest, except for one, remained amenorrheic. We conclude that the use of the resectoscope for endometrial ablation is a successful, efficient, safe, and readily available way to treat intractable uterine bleeding.
Adenosine (ADO) in low micromolar levels and hypoxanthine (HYP) in millimolar levels have been sh... more Adenosine (ADO) in low micromolar levels and hypoxanthine (HYP) in millimolar levels have been shown to inhibit maturation of cumulus-enclosed oocytes. To determine the effect of ovarian stimulation with gonadotrophins on follicular purine metabolism, we measured ADO, HYP, inosine (INO), adenine (ADE) and cyclic AMP (cAMP) levels in follicular fluid (FF) from natural (n = 7) or human menopausal gonadotrophin/human chorionic gonadotrophin (HMG/HCG)-stimulated (n = 35) cycles. Purines were extracted immediately (natural cycles) or within 30 min of recovery (HMG/HCG cycles) and analysed by high pressure liquid chromatography (HPLC). The concentration of all ADE purines in FF was in the low micromolar range (1-20 microM); cAMP levels were markedly increased (greater than 100 microM) in FF of HMG/HCG-treated patients. While ADO levels were within the range effective for inhibition of oocyte maturation, those of HYP were not. No correlation was found between purine levels in FF and ovum m...
Twenty-eight patients participated prospectively in a study to evaluate the impact of hysteroscop... more Twenty-eight patients participated prospectively in a study to evaluate the impact of hysteroscopically detected uterine and cervical anomalies on the success rate of ET in an IVF-ET program. All participants had a normal intrauterine cavity by standard HSG. All the patients had a diagnostic office hysteroscopy under paracervical block before commencing COH. Because our IVF program does not include hysteroscopy as a requirement before undergoing IVF and because the significance of mild intrauterine abnormalities is not yet known, the hysteroscopic findings were not relayed to the personnel involved in the IVF-ET procedure. Sixteen patients (group I) had a normal hysteroscopic evaluation. Twelve patients (group II) had abnormal hysteroscopic findings including small uterine septa, small submucous fibroids, uterine hypoplasia and cervical ridges. Although no difference in patients or cycle characteristics was present, there was a significant difference in the clinical PR between patie...
Insulin and insulin-like growth factors have been implicated in the stimulation of ovarian steroi... more Insulin and insulin-like growth factors have been implicated in the stimulation of ovarian steroidogenesis. To assess the effect of diabetes mellitus on this process, a comparison was made of progesterone production by cultured granulosa cells (50,000 cells/well) from 11 individual follicles of nondiabetic and 6 individual follicles of diabetic women. Diabetic metabolic control was fair [HbA1C 6.8, 8.7 (nl 5.0-7.5)]. Cells were collected by laparoscopic follicular aspiration after ovulation induction and isolated by Percoll gradient centrifugation. Progesterone production was measured after culture with hCG (10 IU/mL) or insulin (100 microU/mL). In both nondiabetic and diabetic groups on day 4, hCG significantly stimulated progesterone production (1,686 +/- 1,268 ng/mL to 4,123 +/- 2,825 ng/mL and 1,059 +/- 249 ng/mL to 1,506 +/- 245 ng/mL, respectively). In nondiabetic follicles, insulin also stimulated progesterone production on days 4 (2366 +/- 1032 ng/mL to 3699 +/- 1582 ng/mL; ...
The Journal of clinical endocrinology and metabolism, 1987
In the in vitro fertilization (IVF) and embryo transfer (ET) program at Yale, 32% of pregnancies ... more In the in vitro fertilization (IVF) and embryo transfer (ET) program at Yale, 32% of pregnancies abort by 16 weeks. With the objective of predicting outcome, serum hCG titers were determined in serial samples from 48 women with clinical pregnancy (conception where fetal sac demonstrated by ultrasound). Although the mean hCG levels were lower at 8-14, 15-21, 22-28 and 29-35 days post-ET in the 18 women who eventually aborted, 0.18 (range 0.01-0.49), 1.5 (0.05-4.7), 6.4 (0.68-27), and 15 nmol/L (0.35-59), respectively, than in the 30 women whose pregnancy went to term, 0.48 (0.01-5.5), 2.2 (0.33-20), 10 (0.46-25), and 116 nmol/L (0.76-335) respectively, the ranges overlapped significantly, limiting the use of serum hCG in prediction. In earlier studies, the free beta-subunit of hCG was demonstrated in the serum of women with natural fertilization pregnancy, 2-6 weeks post ovulation. We used the RIA with 1E5 free beta-subunit monoclonal antibody to measure this component in the IVF ser...
Femoral neuropathy has been reported to occur after abdominal hysterectomies and has been related... more Femoral neuropathy has been reported to occur after abdominal hysterectomies and has been related to nerve compression by abdominal wound retractors. We report a case of a 35-year-old woman with infertility who developed unilateral femoral nerve palsy after laparoscopy and hysteroscopy. This rare complication, secondary to extreme flexion, abduction and lateral rotation of the hip joint, can be prevented by careful preoperative patient positioning.
We have reviewed the pregnancy rate and outcome of 25 patients who underwent tubocornual anastomo... more We have reviewed the pregnancy rate and outcome of 25 patients who underwent tubocornual anastomosis for correction of proximal tubal occlusion at Yale-New Haven Hospital between 1977 and 1981. Tubal occlusion was the result of previous tubal sterilization in 17 patients (11 laparoscopic electrocautery and 6 tubal ligation) and previous tubal infection in 8. Fourteen of the patients conceived (56%). Viable pregnancy was achieved in nine patients (36%) and tubal pregnancy in three (12%). No significant difference in pregnancy rates was found between patients with diseased cornua and those previously sterilized by either electrocautery or tubal ligation. Tubal length of greater than or equal to 4 cm following corrective surgery as compared with less than or equal to 4 cm did not influence pregnancy rates. The patients with the shorter oviducts had a higher rate of early pregnancy wastage. All three tubal pregnancies occurred in patients with reoccluded fallopian tubes as demonstrated by a hysterosalpingogram. We conclude that tubocornual anastomosis still remains the treatment of choice for patients with proximal tubal obstruction.
This study compares the in vitro fertilization and cleavage rates of paired first- and last-recov... more This study compares the in vitro fertilization and cleavage rates of paired first- and last-recovered preovulatory human oocytes that were exposed to a 100% CO2 pneumoperitoneum and general anesthesia. In 305 consecutive cycles of laparoscopy, 1741 oocytes (5.7/cycle) were recovered. The exact time of aspiration (T) was recorded for each oocyte. The time interval (T1 to T2) between recovery of first and last oocytes ranged from 0 to 38 minutes and represented differences in the exposure time of first and last oocytes to the CO2 pneumoperitoneum and to general anesthesia. For all cycles (n = 305) without regard for T1 to T2, last-recovered oocytes fertilized less often than first-recovered eggs (P = 0.06; McNemar's test). When T1 to T2 was short (less than or equal to 5 minutes), first- and last-recovered oocytes fertilized at comparable rates (70.8% and 74.0%). When only cycles with T1 to T2 greater than 5 minutes were considered (n = 209), the difference in fertilization rates ...
The utility of magnetic resonance (MR) imaging in assessing response to therapy with a gonadotrop... more The utility of magnetic resonance (MR) imaging in assessing response to therapy with a gonadotropin-releasing hormone (GnRH) analog was assessed in 19 women with uterine leiomyomas and 19 women with endometriosis. There was a significant reduction in individual fibroid volumes at 3 months (P less than .05) and at 6 months (P less than .005) in the drug group, whereas there was no significant change in the placebo group. Vessel conspicuity significantly decreased at 3 months (P less than .02) and at 6 months (P less than .01) in the drug group but not in the placebo group. In the patients with endometriosis, there was a significant decrease (P less than .0006) in the number of endometriomas visualized. Significant changes were also noted in the pelvis in women who were receiving the GnRH analog. After 6 months of therapy, the identifiability of the ovaries was significantly poorer (P less than .05). The authors conclude that the utility of conservative therapy with a GnRH analog can be quantitatively assessed with MR imaging.
The performance of in vitro fertilization-embryo transfer (IVF-ET) programs is summarized typical... more The performance of in vitro fertilization-embryo transfer (IVF-ET) programs is summarized typically as the average probability of achieving pregnancy per cycle. Variation in conception probabilities across women reduces the usefulness of such an aggregate measure. More relevant is the conditional probability of achieving pregnancy on a given cycle following a number of failed IVF-ET attempts. We construct a model that accurately describes 1,257 treatment cycles performed at Yale over 571 different women. The model assumes a split population, where some women can never conceive via IVF-ET, while the remaining women have identical and constant per cycle probabilities of conception. This model produces estimates that are highly consistent with the data, and suggests that continuing treatment beyond some threshold number of cycles is not efficacious. Recognizing this, we determine cutoffs beyond which treatment should not continue for IVF-ET programs with fixed capacities. We also consider cutoff policies where program participants may belong to one of several different split populations, detailing the case of two groups. Finally, we show how one may reduce the average time in treatment (including waiting time) considerably with minimal impact on the probability of achieving pregnancy.
In contradistinction to other biological systems, the reproductive mechanisms in sexually reprodu... more In contradistinction to other biological systems, the reproductive mechanisms in sexually reproducing species are unique in that their success relies upon a synchronous interaction between two separate individuals. Reproduction has become increasingly more efficient as higher forms have developed internal fertilization and gestation. Although our anthropomorphic perspective has dominated the understanding of reproductive processes, 'recent discoveries' make it clear that this reproductive efficiency has been gained by retention of previously present biological mechanisms whose origins are in the vestigial excretory tracts and ducts which are the precursors of the reproductive tract. We refer to these as 'archetypal systems'. They include the interaction between sex steroid sensitive tissues and sex steroids, the renin-angiotensin system and the macrophage/monokine response to infection. Through these mechanisms the reproductive tracts have maintained control over the microenvironment in which the reproductive processes occur. Thus, gamete development in male and female, and fertilization and early embryonic existence in the female tract prior to implantation still occur in compartments which are extracorporeal, i.e., separated from blood or subendothelial spaces, and are controlled by cellular mechanisms found in ancient excretory tracts. Since the majority of the changes between lower forms and contemporary mammals are anatomical modifications which have favoured the success of these extracorporeal events within the developing, generally land-based mammals, we should take special note of lower animals, understanding the evolutionary appropriation of mechanisms designed to furnish the suitable microenvironment from the surrounding tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
To determine if the timing of the onset of pituitary desensitization and ovarian suppression usin... more To determine if the timing of the onset of pituitary desensitization and ovarian suppression using follicular phase leuprolide acetate (LA) is associated with in vitro fertilization-embryo transfer (IVF-ET) success for pregnancy. Retrospective series of IVF patients undergoing pituitary desensitization and ovarian suppression before beginning controlled ovarian hyperstimulation for IVF-ET. Tertiary infertility practice. Seventy-eight women for 80 cycles began LA on day 1 of their menstrual cycle. After 11 days of LA, 47 (59%) cycles in group I had suppressed serum estradiol (E2) levels less than 40 pg/mL, in contrast to 33 (41%) cycles in group II not adequately suppressed, thereby requiring additional days to achieve suppression. Controlled ovarian hyperstimulation was started when patients were satisfactorily suppressed, i.e., E2 less than 40 pg/mL. Mean E2 response, ampules of human menopausal gonadotropin, cancellation rates, number of oocytes retrieved, fertilization rates, and...
Twenty-one patients with intractable uterine bleeding were treated by resectoscopic ablation of t... more Twenty-one patients with intractable uterine bleeding were treated by resectoscopic ablation of the endometrium. All the patients were worked up thoroughly to rule out hormonal or anatomic reasons for their bleeding. In addition, various hormonal regimens were tried to stop the bleeding. Our technique used the modified urologic resectoscope, which is inserted into the uterine cavity. The entire endometrial cavity was ablated using 30 W of coagulating current. Of the 21 patients treated, 14 had blood dyscrasias, four were poor anesthetic risks, and three refused hysterectomy. There were no complications from the procedure. Three patients died from their primary disease, and all the rest, except for one, remained amenorrheic. We conclude that the use of the resectoscope for endometrial ablation is a successful, efficient, safe, and readily available way to treat intractable uterine bleeding.
Adenosine (ADO) in low micromolar levels and hypoxanthine (HYP) in millimolar levels have been sh... more Adenosine (ADO) in low micromolar levels and hypoxanthine (HYP) in millimolar levels have been shown to inhibit maturation of cumulus-enclosed oocytes. To determine the effect of ovarian stimulation with gonadotrophins on follicular purine metabolism, we measured ADO, HYP, inosine (INO), adenine (ADE) and cyclic AMP (cAMP) levels in follicular fluid (FF) from natural (n = 7) or human menopausal gonadotrophin/human chorionic gonadotrophin (HMG/HCG)-stimulated (n = 35) cycles. Purines were extracted immediately (natural cycles) or within 30 min of recovery (HMG/HCG cycles) and analysed by high pressure liquid chromatography (HPLC). The concentration of all ADE purines in FF was in the low micromolar range (1-20 microM); cAMP levels were markedly increased (greater than 100 microM) in FF of HMG/HCG-treated patients. While ADO levels were within the range effective for inhibition of oocyte maturation, those of HYP were not. No correlation was found between purine levels in FF and ovum m...
Twenty-eight patients participated prospectively in a study to evaluate the impact of hysteroscop... more Twenty-eight patients participated prospectively in a study to evaluate the impact of hysteroscopically detected uterine and cervical anomalies on the success rate of ET in an IVF-ET program. All participants had a normal intrauterine cavity by standard HSG. All the patients had a diagnostic office hysteroscopy under paracervical block before commencing COH. Because our IVF program does not include hysteroscopy as a requirement before undergoing IVF and because the significance of mild intrauterine abnormalities is not yet known, the hysteroscopic findings were not relayed to the personnel involved in the IVF-ET procedure. Sixteen patients (group I) had a normal hysteroscopic evaluation. Twelve patients (group II) had abnormal hysteroscopic findings including small uterine septa, small submucous fibroids, uterine hypoplasia and cervical ridges. Although no difference in patients or cycle characteristics was present, there was a significant difference in the clinical PR between patie...
Insulin and insulin-like growth factors have been implicated in the stimulation of ovarian steroi... more Insulin and insulin-like growth factors have been implicated in the stimulation of ovarian steroidogenesis. To assess the effect of diabetes mellitus on this process, a comparison was made of progesterone production by cultured granulosa cells (50,000 cells/well) from 11 individual follicles of nondiabetic and 6 individual follicles of diabetic women. Diabetic metabolic control was fair [HbA1C 6.8, 8.7 (nl 5.0-7.5)]. Cells were collected by laparoscopic follicular aspiration after ovulation induction and isolated by Percoll gradient centrifugation. Progesterone production was measured after culture with hCG (10 IU/mL) or insulin (100 microU/mL). In both nondiabetic and diabetic groups on day 4, hCG significantly stimulated progesterone production (1,686 +/- 1,268 ng/mL to 4,123 +/- 2,825 ng/mL and 1,059 +/- 249 ng/mL to 1,506 +/- 245 ng/mL, respectively). In nondiabetic follicles, insulin also stimulated progesterone production on days 4 (2366 +/- 1032 ng/mL to 3699 +/- 1582 ng/mL; ...
The Journal of clinical endocrinology and metabolism, 1987
In the in vitro fertilization (IVF) and embryo transfer (ET) program at Yale, 32% of pregnancies ... more In the in vitro fertilization (IVF) and embryo transfer (ET) program at Yale, 32% of pregnancies abort by 16 weeks. With the objective of predicting outcome, serum hCG titers were determined in serial samples from 48 women with clinical pregnancy (conception where fetal sac demonstrated by ultrasound). Although the mean hCG levels were lower at 8-14, 15-21, 22-28 and 29-35 days post-ET in the 18 women who eventually aborted, 0.18 (range 0.01-0.49), 1.5 (0.05-4.7), 6.4 (0.68-27), and 15 nmol/L (0.35-59), respectively, than in the 30 women whose pregnancy went to term, 0.48 (0.01-5.5), 2.2 (0.33-20), 10 (0.46-25), and 116 nmol/L (0.76-335) respectively, the ranges overlapped significantly, limiting the use of serum hCG in prediction. In earlier studies, the free beta-subunit of hCG was demonstrated in the serum of women with natural fertilization pregnancy, 2-6 weeks post ovulation. We used the RIA with 1E5 free beta-subunit monoclonal antibody to measure this component in the IVF ser...
Femoral neuropathy has been reported to occur after abdominal hysterectomies and has been related... more Femoral neuropathy has been reported to occur after abdominal hysterectomies and has been related to nerve compression by abdominal wound retractors. We report a case of a 35-year-old woman with infertility who developed unilateral femoral nerve palsy after laparoscopy and hysteroscopy. This rare complication, secondary to extreme flexion, abduction and lateral rotation of the hip joint, can be prevented by careful preoperative patient positioning.
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Papers by Gad Lavy