Fertility after tubal ligation – It’s a matter of ‘AGE’

Despite the original intent of permanent contraception, tubal sterilization regret is experienced by 2%-26% of women as demonstrated by the United States Collaborative Review of Sterilization “CREST” 14-year study (Obstet Gynecol. 1999 Jun;93[6]:889-95). Regret appears to be higher in the United States than Europe and in resource-limited countries and is more common in women who are less than age 30, African-American, and unmarried. Nevertheless, requests for tubal reversal are estimated to be between 1% and 4% (Contraception. 1981 Jun;23[6]:579-89). The alternative option for fertility is in vitro fertilization (IVF) and this month’s column considers the pros and cons of both methods.

The procedure of tubal reanastomosis involves removing abnormal tissue and reapproximating the healthy tubal segments with attention to minimize adhesion formation through continued gentle irrigation. The surgery involves microsuturing using 6-0 to 10-0 sutures. Tubal patency can be confirmed during the procedure and with a subsequent hysterosalpingogram. While time from sterilization and the type of sterilization technique are factors that may influence the success rate of tubal reanastomosis, the age of the woman is the most predictive for pregnancy outcome.

In the original CREST study, the risk of ectopic pregnancy following tubal reanastomosis was contingent on the method of sterilization: Bipolar electrosurgery resulted in the highest probability of ectopic pregnancy (17.1 per 1,000 procedures at 10 years after permanent contraception), while postpartum partial salpingectomy resulted in the lowest (1.5 per 1,000 procedures at 10 years after permanent contraception) (N Engl J Med. 1997;336[11]:762). Comparatively, the ectopic pregnancy rate during an IVF cycle was 1.9% for pregnancies from transfers of fresh cleavage embryo, followed by transfers of frozen cleavage embryo (1.7%), transfers of fresh blastocyst (1.3%), and transfers of frozen blastocyst (0.8%) (Hum Reprod. 2015;30[9]:2048-54).

Reports vary regarding pregnancy rates from tubal reanastomosis. Prior use of rings and clips for sterilization appear to yield the highest outcomes as opposed to the use of electrocautery. In one large Canadian cohort study of over 300,000 women, those aged 15-30 years, 30-33 years, and 34-49 years had a conception rate of 73%, 64%, and 46%, respectively (Obstet Gynecol. 2003;101[4]:677-84). Most pregnancies were within 2 years after reversal and 48% of women achieved a delivery. Of interest, 23% of patients subsequently underwent another sterilization.

An Australian study of nearly 2,000 women found an overall cumulative live-delivery rate of 20% within the first year after reversal, 40% at 2 years, 51% at 5 years, and 52% at 10 years. As expected, the 5-year cumulative live-delivery rate was significantly lower in women who were aged 40-44 years (26%), compared with younger women. For all women below age 40 years, the live-delivery rate was approximately 50% within 5 years after tubal reanastomosis, while the rate halves after the age of 40 (Fertil Steril. 2015 Oct;104[4]:921-6).

To compare tubal reanastomosis with IVF, a retrospective cohort study of 163 patients demonstrated the cumulative delivery rate over 72 months was comparable for IVF vs. sterilization reversal (52% vs. 60%). The only significant difference was in a subset of patients aged <37 years (52% after IVF and 72% after reversal) and the lower cost of surgery. The authors advocated laparoscopic sterilization reversal in women younger than 37 years who have ≥4 cm of residual tube with IVF as the better alternative for all other women (Hum Reprod. 2007;22[10]:2660).

Indeed, tubal length is another important factor in successful reversal. The pregnancy rate after tubal anastomosis is 75% in women with tubal length of 4 cm or more, but only 19% in those with shorter tubes (Fertil Steril. 1987;48[1]:13-7). The literature does suggest equivalent pregnancy rates after laparoscopic tubal anastomosis and conventional microsurgical anastomosis. Although the laparoscopic approach may be more economical, it is more demanding technically than an open microsurgical procedure.

Tubal reanastomosis can also be performed using robot-assisted laparoscopy. In preliminary studies, robotic surgery appears to have a similar success rate and a shorter recovery time, but longer operative times and higher costs (Obstet Gynecol. 2007;109[6]:1375; Fertil Steril. 2008;90[4]:1175).

To educate women on the success of IVF based on individual characteristics, a valuable tool to approximate the cumulative outcome for a live birth following one cycle of IVF is offered by the Society for Assisted Reproductive Technology. To clarify, a cycle of IVF consists of one egg retrieval and the ultimate transfer of all embryos produced, i.e., fresh and frozen. The website also includes estimations of success following a second and third IVF cycle.

The woman’s age is a significant predictor of IVF success. Ovarian aging is currently best measured by combining chronologic age, antral follicle count (AFC) by transvaginal pelvic ultrasound, and serum anti-Müllerian hormone (AMH). Natural fecundity begins to decline, on average, above age 32-33 years. An AFC less than 11 reflects diminished ovarian reserve (DOR) and less than 6 is severe. AMH levels below 1.6 ng/mL have been shown to reduce the number of eggs retrieved with IVF, while levels below 0.4 ng/mL are very low. Very low AMH levels negatively affect the outcome of IVF cycles as demonstrated in the SART data study from a population of women with a mean age of 39.4 years: Cycle cancellation was 54%; of all retrieval attempts, no oocytes were obtained in 5.4%, and no embryo transfer occurred in 25.1% of cycles; the live birth rate per embryo transfer was 20.5% (9.5% per cycle start and 16.3% per retrieval) from a mean age of 36.8 years (Fertil Steril. 2016 Feb;105[2]:385-93.e3). The predictive ability of AMH on the live birth rate from IVF cycles was also shown in a study of over 85,000 women (Fertil Steril. 2018;109:258-65).

While low AMH has been shown to lessen a successful outcome from IVF, there appears to be no difference in natural pregnancy rates in women aged 30-44 years irrespective of AMH levels (JAMA. 2017;318[14]:1367-76). Of importance, the use of AMH in a population at low risk for DOR will yield a larger number of false-positive results (i.e., characterizing a woman as DOR when in fact she has normal ovarian reserve). Further, users of hormonal contraceptives have a 25.2% lower mean AMH level than nonusers.

When a patient is considering tubal reanastomosis vs. IVF, a useful acronym to remember is to check “AGE” – the A is for AMH because severely diminished ovarian reserve will reduce success with IVF as shown by the SART calculator; the G represents guy, i.e., ensuring a reasonably normal sperm analysis; and E stands for eggs representing ovulation function. In a woman who is anovulatory and who will require fertility medication, it would be reasonable to consider IVF given the need for ovarian stimulation. As in females, advanced paternal age has demonstrated a decline in fertility and sperm analysis parameters. Men above age 45 take approximately five times as long to achieve a pregnancy, compared with men less than 25 years of age. Further, there is evidence for advanced paternal age increasing risk of miscarriage, preterm birth, and birth defects. Men older than 40-45 years have twice the risk of an autistic child and five times the risk of having a child with schizophrenia (Transl Psychiatry 2017;7: e1019; Am J Psychiatry. 2002;159:1528-33).

To conclude, the data support consideration for sterilization reversal in women less than age 37 years with more than 4 cm of residual functional fallopian tube and the prior use of rings or clip sterilization. In other women, IVF may be the better option, particularly when ovulation dysfunction and/or male factor is present. IVF also offers the advantage of maintaining contraception and gender determination. However, given that AMH does not appear to reduce natural fertility, unlike during its effect during an IVF cycle, the option of tubal reversal may be more favorable in women with severe DOR.

Dr. Trolice is director of the IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.

Despite the original intent of permanent contraception, tubal sterilization regret is experienced by 2%-26% of women as demonstrated by the United States Collaborative Review of Sterilization “CREST” 14-year study (Obstet Gynecol. 1999 Jun;93[6]:889-95). Regret appears to be higher in the United States than Europe and in resource-limited countries and is more common in women who are less than age 30, African-American, and unmarried. Nevertheless, requests for tubal reversal are estimated to be between 1% and 4% (Contraception. 1981 Jun;23[6]:579-89). The alternative option for fertility is in vitro fertilization (IVF) and this month’s column considers the pros and cons of both methods.

The procedure of tubal reanastomosis involves removing abnormal tissue and reapproximating the healthy tubal segments with attention to minimize adhesion formation through continued gentle irrigation. The surgery involves microsuturing using 6-0 to 10-0 sutures. Tubal patency can be confirmed during the procedure and with a subsequent hysterosalpingogram. While time from sterilization and the type of sterilization technique are factors that may influence the success rate of tubal reanastomosis, the age of the woman is the most predictive for pregnancy outcome.

In the original CREST study, the risk of ectopic pregnancy following tubal reanastomosis was contingent on the method of sterilization: Bipolar electrosurgery resulted in the highest probability of ectopic pregnancy (17.1 per 1,000 procedures at 10 years after permanent contraception), while postpartum partial salpingectomy resulted in the lowest (1.5 per 1,000 procedures at 10 years after permanent contraception) (N Engl J Med. 1997;336[11]:762). Comparatively, the ectopic pregnancy rate during an IVF cycle was 1.9% for pregnancies from transfers of fresh cleavage embryo, followed by transfers of frozen cleavage embryo (1.7%), transfers of fresh blastocyst (1.3%), and transfers of frozen blastocyst (0.8%) (Hum Reprod. 2015;30[9]:2048-54).

Reports vary regarding pregnancy rates from tubal reanastomosis. Prior use of rings and clips for sterilization appear to yield the highest outcomes as opposed to the use of electrocautery. In one large Canadian cohort study of over 300,000 women, those aged 15-30 years, 30-33 years, and 34-49 years had a conception rate of 73%, 64%, and 46%, respectively (Obstet Gynecol. 2003;101[4]:677-84). Most pregnancies were within 2 years after reversal and 48% of women achieved a delivery. Of interest, 23% of patients subsequently underwent another sterilization.

An Australian study of nearly 2,000 women found an overall cumulative live-delivery rate of 20% within the first year after reversal, 40% at 2 years, 51% at 5 years, and 52% at 10 years. As expected, the 5-year cumulative live-delivery rate was significantly lower in women who were aged 40-44 years (26%), compared with younger women. For all women below age 40 years, the live-delivery rate was approximately 50% within 5 years after tubal reanastomosis, while the rate halves after the age of 40 (Fertil Steril. 2015 Oct;104[4]:921-6).

To compare tubal reanastomosis with IVF, a retrospective cohort study of 163 patients demonstrated the cumulative delivery rate over 72 months was comparable for IVF vs. sterilization reversal (52% vs. 60%). The only significant difference was in a subset of patients aged <37 years (52% after IVF and 72% after reversal) and the lower cost of surgery. The authors advocated laparoscopic sterilization reversal in women younger than 37 years who have ≥4 cm of residual tube with IVF as the better alternative for all other women (Hum Reprod. 2007;22[10]:2660).

Indeed, tubal length is another important factor in successful reversal. The pregnancy rate after tubal anastomosis is 75% in women with tubal length of 4 cm or more, but only 19% in those with shorter tubes (Fertil Steril. 1987;48[1]:13-7). The literature does suggest equivalent pregnancy rates after laparoscopic tubal anastomosis and conventional microsurgical anastomosis. Although the laparoscopic approach may be more economical, it is more demanding technically than an open microsurgical procedure.

Tubal reanastomosis can also be performed using robot-assisted laparoscopy. In preliminary studies, robotic surgery appears to have a similar success rate and a shorter recovery time, but longer operative times and higher costs (Obstet Gynecol. 2007;109[6]:1375; Fertil Steril. 2008;90[4]:1175).

To educate women on the success of IVF based on individual characteristics, a valuable tool to approximate the cumulative outcome for a live birth following one cycle of IVF is offered by the Society for Assisted Reproductive Technology. To clarify, a cycle of IVF consists of one egg retrieval and the ultimate transfer of all embryos produced, i.e., fresh and frozen. The website also includes estimations of success following a second and third IVF cycle.

The woman’s age is a significant predictor of IVF success. Ovarian aging is currently best measured by combining chronologic age, antral follicle count (AFC) by transvaginal pelvic ultrasound, and serum anti-Müllerian hormone (AMH). Natural fecundity begins to decline, on average, above age 32-33 years. An AFC less than 11 reflects diminished ovarian reserve (DOR) and less than 6 is severe. AMH levels below 1.6 ng/mL have been shown to reduce the number of eggs retrieved with IVF, while levels below 0.4 ng/mL are very low. Very low AMH levels negatively affect the outcome of IVF cycles as demonstrated in the SART data study from a population of women with a mean age of 39.4 years: Cycle cancellation was 54%; of all retrieval attempts, no oocytes were obtained in 5.4%, and no embryo transfer occurred in 25.1% of cycles; the live birth rate per embryo transfer was 20.5% (9.5% per cycle start and 16.3% per retrieval) from a mean age of 36.8 years (Fertil Steril. 2016 Feb;105[2]:385-93.e3). The predictive ability of AMH on the live birth rate from IVF cycles was also shown in a study of over 85,000 women (Fertil Steril. 2018;109:258-65).

While low AMH has been shown to lessen a successful outcome from IVF, there appears to be no difference in natural pregnancy rates in women aged 30-44 years irrespective of AMH levels (JAMA. 2017;318[14]:1367-76). Of importance, the use of AMH in a population at low risk for DOR will yield a larger number of false-positive results (i.e., characterizing a woman as DOR when in fact she has normal ovarian reserve). Further, users of hormonal contraceptives have a 25.2% lower mean AMH level than nonusers.

When a patient is considering tubal reanastomosis vs. IVF, a useful acronym to remember is to check “AGE” – the A is for AMH because severely diminished ovarian reserve will reduce success with IVF as shown by the SART calculator; the G represents guy, i.e., ensuring a reasonably normal sperm analysis; and E stands for eggs representing ovulation function. In a woman who is anovulatory and who will require fertility medication, it would be reasonable to consider IVF given the need for ovarian stimulation. As in females, advanced paternal age has demonstrated a decline in fertility and sperm analysis parameters. Men above age 45 take approximately five times as long to achieve a pregnancy, compared with men less than 25 years of age. Further, there is evidence for advanced paternal age increasing risk of miscarriage, preterm birth, and birth defects. Men older than 40-45 years have twice the risk of an autistic child and five times the risk of having a child with schizophrenia (Transl Psychiatry 2017;7: e1019; Am J Psychiatry. 2002;159:1528-33).

To conclude, the data support consideration for sterilization reversal in women less than age 37 years with more than 4 cm of residual functional fallopian tube and the prior use of rings or clip sterilization. In other women, IVF may be the better option, particularly when ovulation dysfunction and/or male factor is present. IVF also offers the advantage of maintaining contraception and gender determination. However, given that AMH does not appear to reduce natural fertility, unlike during its effect during an IVF cycle, the option of tubal reversal may be more favorable in women with severe DOR.

Dr. Trolice is director of the IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.

Despite the original intent of permanent contraception, tubal sterilization regret is experienced by 2%-26% of women as demonstrated by the United States Collaborative Review of Sterilization “CREST” 14-year study (Obstet Gynecol. 1999 Jun;93[6]:889-95). Regret appears to be higher in the United States than Europe and in resource-limited countries and is more common in women who are less than age 30, African-American, and unmarried. Nevertheless, requests for tubal reversal are estimated to be between 1% and 4% (Contraception. 1981 Jun;23[6]:579-89). The alternative option for fertility is in vitro fertilization (IVF) and this month’s column considers the pros and cons of both methods.

The procedure of tubal reanastomosis involves removing abnormal tissue and reapproximating the healthy tubal segments with attention to minimize adhesion formation through continued gentle irrigation. The surgery involves microsuturing using 6-0 to 10-0 sutures. Tubal patency can be confirmed during the procedure and with a subsequent hysterosalpingogram. While time from sterilization and the type of sterilization technique are factors that may influence the success rate of tubal reanastomosis, the age of the woman is the most predictive for pregnancy outcome.

In the original CREST study, the risk of ectopic pregnancy following tubal reanastomosis was contingent on the method of sterilization: Bipolar electrosurgery resulted in the highest probability of ectopic pregnancy (17.1 per 1,000 procedures at 10 years after permanent contraception), while postpartum partial salpingectomy resulted in the lowest (1.5 per 1,000 procedures at 10 years after permanent contraception) (N Engl J Med. 1997;336[11]:762). Comparatively, the ectopic pregnancy rate during an IVF cycle was 1.9% for pregnancies from transfers of fresh cleavage embryo, followed by transfers of frozen cleavage embryo (1.7%), transfers of fresh blastocyst (1.3%), and transfers of frozen blastocyst (0.8%) (Hum Reprod. 2015;30[9]:2048-54).

Reports vary regarding pregnancy rates from tubal reanastomosis. Prior use of rings and clips for sterilization appear to yield the highest outcomes as opposed to the use of electrocautery. In one large Canadian cohort study of over 300,000 women, those aged 15-30 years, 30-33 years, and 34-49 years had a conception rate of 73%, 64%, and 46%, respectively (Obstet Gynecol. 2003;101[4]:677-84). Most pregnancies were within 2 years after reversal and 48% of women achieved a delivery. Of interest, 23% of patients subsequently underwent another sterilization.

An Australian study of nearly 2,000 women found an overall cumulative live-delivery rate of 20% within the first year after reversal, 40% at 2 years, 51% at 5 years, and 52% at 10 years. As expected, the 5-year cumulative live-delivery rate was significantly lower in women who were aged 40-44 years (26%), compared with younger women. For all women below age 40 years, the live-delivery rate was approximately 50% within 5 years after tubal reanastomosis, while the rate halves after the age of 40 (Fertil Steril. 2015 Oct;104[4]:921-6).

To compare tubal reanastomosis with IVF, a retrospective cohort study of 163 patients demonstrated the cumulative delivery rate over 72 months was comparable for IVF vs. sterilization reversal (52% vs. 60%). The only significant difference was in a subset of patients aged <37 years (52% after IVF and 72% after reversal) and the lower cost of surgery. The authors advocated laparoscopic sterilization reversal in women younger than 37 years who have ≥4 cm of residual tube with IVF as the better alternative for all other women (Hum Reprod. 2007;22[10]:2660).

Indeed, tubal length is another important factor in successful reversal. The pregnancy rate after tubal anastomosis is 75% in women with tubal length of 4 cm or more, but only 19% in those with shorter tubes (Fertil Steril. 1987;48[1]:13-7). The literature does suggest equivalent pregnancy rates after laparoscopic tubal anastomosis and conventional microsurgical anastomosis. Although the laparoscopic approach may be more economical, it is more demanding technically than an open microsurgical procedure.

Tubal reanastomosis can also be performed using robot-assisted laparoscopy. In preliminary studies, robotic surgery appears to have a similar success rate and a shorter recovery time, but longer operative times and higher costs (Obstet Gynecol. 2007;109[6]:1375; Fertil Steril. 2008;90[4]:1175).

To educate women on the success of IVF based on individual characteristics, a valuable tool to approximate the cumulative outcome for a live birth following one cycle of IVF is offered by the Society for Assisted Reproductive Technology. To clarify, a cycle of IVF consists of one egg retrieval and the ultimate transfer of all embryos produced, i.e., fresh and frozen. The website also includes estimations of success following a second and third IVF cycle.

The woman’s age is a significant predictor of IVF success. Ovarian aging is currently best measured by combining chronologic age, antral follicle count (AFC) by transvaginal pelvic ultrasound, and serum anti-Müllerian hormone (AMH). Natural fecundity begins to decline, on average, above age 32-33 years. An AFC less than 11 reflects diminished ovarian reserve (DOR) and less than 6 is severe. AMH levels below 1.6 ng/mL have been shown to reduce the number of eggs retrieved with IVF, while levels below 0.4 ng/mL are very low. Very low AMH levels negatively affect the outcome of IVF cycles as demonstrated in the SART data study from a population of women with a mean age of 39.4 years: Cycle cancellation was 54%; of all retrieval attempts, no oocytes were obtained in 5.4%, and no embryo transfer occurred in 25.1% of cycles; the live birth rate per embryo transfer was 20.5% (9.5% per cycle start and 16.3% per retrieval) from a mean age of 36.8 years (Fertil Steril. 2016 Feb;105[2]:385-93.e3). The predictive ability of AMH on the live birth rate from IVF cycles was also shown in a study of over 85,000 women (Fertil Steril. 2018;109:258-65).

While low AMH has been shown to lessen a successful outcome from IVF, there appears to be no difference in natural pregnancy rates in women aged 30-44 years irrespective of AMH levels (JAMA. 2017;318[14]:1367-76). Of importance, the use of AMH in a population at low risk for DOR will yield a larger number of false-positive results (i.e., characterizing a woman as DOR when in fact she has normal ovarian reserve). Further, users of hormonal contraceptives have a 25.2% lower mean AMH level than nonusers.

When a patient is considering tubal reanastomosis vs. IVF, a useful acronym to remember is to check “AGE” – the A is for AMH because severely diminished ovarian reserve will reduce success with IVF as shown by the SART calculator; the G represents guy, i.e., ensuring a reasonably normal sperm analysis; and E stands for eggs representing ovulation function. In a woman who is anovulatory and who will require fertility medication, it would be reasonable to consider IVF given the need for ovarian stimulation. As in females, advanced paternal age has demonstrated a decline in fertility and sperm analysis parameters. Men above age 45 take approximately five times as long to achieve a pregnancy, compared with men less than 25 years of age. Further, there is evidence for advanced paternal age increasing risk of miscarriage, preterm birth, and birth defects. Men older than 40-45 years have twice the risk of an autistic child and five times the risk of having a child with schizophrenia (Transl Psychiatry 2017;7: e1019; Am J Psychiatry. 2002;159:1528-33).

To conclude, the data support consideration for sterilization reversal in women less than age 37 years with more than 4 cm of residual functional fallopian tube and the prior use of rings or clip sterilization. In other women, IVF may be the better option, particularly when ovulation dysfunction and/or male factor is present. IVF also offers the advantage of maintaining contraception and gender determination. However, given that AMH does not appear to reduce natural fertility, unlike during its effect during an IVF cycle, the option of tubal reversal may be more favorable in women with severe DOR.

Dr. Trolice is director of the IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.