| Background In recent years,because of social stress,living environment,cancer,the birth of two children's policies and the impact of the loss of children's family,more and more women want to have children in the elderly,which makes the incidence of women's diminished ovarian reserve increasing.Therefore,in the assisted reproductive treatment process,the incidence of poor ovarian response was also getting higher.Currently in our country,what kind of regimen for patients with poor ovarian response more effective,more economical,more secure was inconsistent.The clinical outcomes of patients with poor ovarian response were analyzed retrospectively.It will help to improve the clinical treatment.Clinical information1 Object of study The data for this study were retrieved from patient's medical records from January 2012 to June 2016.Nine hundred and eighty-nine cycles were enrolled from our computerized IVF database.The mean age of the patients was 37.68 ±5.21 years.We selected patients according to the European Society of human reproduction and embryology.Inclusion criteria: the patients had at least two of the following characteristics;?1?Advanced maternal age??40 years old?;?2?A history of poor ovarian response,once used conventional ovulation induction of oocytes <3;?3?An abnormal ovarian reserve test?antral follicle count of <5-7 follicles?.Two episodes of POR after maximal stimulation are sufficient to define a patient as a poor responder.The exclusion criteria are as follows:?1?Does not meet the criteria;?2?For individual reasons,during the ovulation induction cycle,the oocyte withdrawal program was cancelled;?3?Some uterine diseases seriously affect the endometrial environment,including severe endometriosis,endometrial hyperplasia or tuberculosis,uterine effusion or severe adhesion;?4?The man suffers from retrograde ejaculation,azoospermia,and need to have a epididymal or testicular needle;?5?The patients with premature ovarian failure who received donate oocyte,and the infertile man who received donate sperm.Any of the above is excluded.2 Grouping criteria The patients were divided into 3 groups according to their ages.A group: the age of patient<35 years;B group;the age of patient between 36 to 39 years;C group: the age of patient>40 years.According to the previous pregnancy,the patients were divided into two groups: The patient had no history of pregnancy,referred to as the primary infertility group;The patient had a history of birth or miscarriage,referred to as secondary infertility group.The patients were divided into groups according to whether ovulation was used: The ovulation inducing drugs were divided into one group,and the ovulation free drugs were divided into one group.The group using the drug for superovulation was designated as the COH group,and the group using natural ovulation cycle instead of superovulation was designated as the NC group.According to the COH scheme,they were divided into four groups: Group 1 was GnRH-a long protocol group,group 2 was GnRH-a antagonist protocol group,group 3 was micro-stimulation protocol group,and group4 was GnRH-a short protocol group.Group 1 was GnRH-a long protocol group.GnRH analogues was using in 7 days after ovulation began in the mid luteal phase of the menstrual period.When reach the standard range,Gn were used.According to B-monitoring,the dosage was adjusted to HCG injection day.The standard: the endometrial thickness was less than 5mm,the E2 value is less than 50pg/ml,the P value is less than lng/ml,the FSH and LH are less than 5mIU/ml.Group 2 was GnRH-a antagonist protocol group.On Day 2 of the menstrual cycle,Gn were commenced.When the leading follicle exceeded 13 mm indiameter, GnRH antagonist was started daily until the day of HCG administration.Group 3 was micro-stimulation protocol group.On Day 2 of the menstrual cycle,Gn were commenced.According to B-monitoring;the dosage was adjusted to HCG injection day.Group4 was GnRH-a short protocol group.On Day 2 of the menstrual cycle,GnRH-a and Gn were commenced.According to B-monitoring,the dosage was adjusted to HCG injection day.3 Statistical methods The results were presented as mean ± SD??± s?or rate?%?.The data were analyzed by the one-way analysis of variance method or non-parametric test.Chi-square or Fisher's exact tests were used to analyze the clinical pregnancy rate,implantation rate and miscarriage rate.SPSS 18.0 statistical software was used,P<0.05 was statistically significant.Results1 Analysis of overall pregnancy outcome of patients with poor ovarian response From January 2012 to June 2016,A total of 989 cycles with poor ovarian responses had been chosen according to the criteria of this study.The mean female age in the study was 37.68±5.21 years.The average duration of infertility was4.69±3.79 years.The mean body mass index were 24.26±3.1 Okg/m.The number of oocyte retrieval cycles was 873 cycles.The average number of oocytes was3.13±2.32.The transplant cycles number was 324.562 embryos were transferred.The average number of embryos transferred was 1.73±0.58.There were 94 pregnancy cycle.The total clinical pregnancy rate was 29.01%.There were 115 implanted embryos.There were two ectopic pregnancy.The total embryo implantation rate was 20.46%.2 According to the age of the patients According to the age of the patients,they were divided into three groups.A group:the age of patient <35 years old,the cycles was 288 account for 29.12%.B group:the age of patient between 36 and 39 years old,the number of cycles was 285 account for 28.82%.C group: the age of patient >40 years old,the number of cycles was 416 account for 29.12%.The cycles in C group are highest.The mean body mass index were 23.23±3.16 kg/m2?24.38±3.02kg/m2?24.90±2.96 kg/m2,respectively.The difference between the three groups was statistically significant?P<0.01?,and showed an increasing trend with age.Average number of ovums obtained: Group A was 3.38±3.3;group B was3.11 ±2.56;group C was 2.50±2.33.There was statistical difference between the 3group?P < 0.01?.The average number of ovums in the C group was the least,the older the age,the fewer the ovums were obtained.The number of transfer cycles were 115?86 and 123.The average number of embryos transferred were 1.70±0.48?1.78±0.61?1.73±0.65.The clinical pregnancy rates were 43.48%,33.72% and 12.20% respectively.There was statistical difference between 3 groups?P<0.01?.Overall pregnancy rate decreased with age,and pregnancy rate was lowest in group C.The number of implantation embryos in the three groups was A group,65 gestational sacs,B group 33 gestational sacs and C group 17 gestational sacs.The implantation rates were 33.16%,21.57% and7.98% respectively,and the differences were statistically significant?P<0.01?.With the increase of age,the rate of implantation decreased,and the rate of implantation in group A was the highest,and the rate of implantation in C group was lowest.Three groups of abortion A group cycles were 7 cycles,9 cycles of B group and C group for 8 cycles,the abortion rate was 14%,31.03%,53.33%,the differences were statistically significant?P<0.05?.3 Analysis of pregnancy outcomes based on previous pregnancy scenarios According to the previous pregnancy group,there are 244 cycles in the primary infertility group,accounting for 24.67%,745 cycles in secondary infertility group,accounting for 75.37%.The average age of the two groups was 33.59± 4.94 and 39.02± 4.56,respectively.The body mass index was 23.32± 3 kg/m2 and24.57±3.09 kg/m2,the difference was statistically significant?P<0.01?.The secondary infertility group had higher age and heavier weight.The number of transfer cycles in the two groups was 83 cycles and 241 cycles, respectively,and the total number of embryos was 143 and 419,respectively.The average number of embryos were 1.72 ± 0.53 and 1.74± 0.60,the number of pregnancy of the two groups were primary infertility group of 34 cycles,the secondary infertility group of 60 cycles,the clinical pregnancy rates were 40.96%and 24.90%,between the two groups was statistically significant?P<0.01?.The pregnancy rate was higher in the primary infertility group.The number of implantation embryos in the two groups was 44 gestational sacs and 71 gestational sacs,the implantation rate was 30.77% and 16.95%,respectively,and the difference was statistically significant?P<0.01?.The rate of implantation was higher in primary infertility group.The rate of abortion in the two groups was 11.77% and33.33% respectively,the difference was statistically significant?P=0.017?,and the rate of abortion was higher in secondary infertility group.The clinical pregnancyrate,implantation rate and abortion rate were compared between the cases of under the age of 35 years old among the 2 group.The clinical outcome of patients under35 years of age was analyzed the 2 group,with pregnancy rates of 44.07% and42.86%,respectively.The implantation rates were 35.35% and 31.96%,respectively.The abortion rates were 3.85% and 25%,respectively.Statistical analysis showed no difference?P>0.05?.4 Analysis of pregnancy outcomes according to whether ovulation induction drugs were used In the 989 cycles,there are 807 cycles used ovulation induction,and the natural cycle was 182 cycles.There was no statistical difference between the two groups in basic values?P>0.05?.The average number of ovums was 5.03± 4.36 and0.76±0.58,and the difference between the two groups was statistically significant?P<0.01?.The number of oocytes obtained in the natural cycle group was less than that in the ovulation induction group.The number of cycles in the COH group is 288 cycles and in the NC cycle group is 36 cycles.The total number of embryos transferred was 522 and 40,respectively.The average number of embryos transferred was 1.81 ± 0.56 and 1.11±0.32,respectively.There were differences in statistical analysis?P<0.01?.The number of transplanted embryos in ovulation induction group was higher than that in natural cycle group.The number of pregnancies in the two groups was 87 cycles in the COH group and 7 cycles in the NC group.The pregnancy rates were 30.21%and 19.44%,respectively,and there was no significant difference between the two groups?P=0.180?,The number of implantation embryos in the two groups was 109 gestational sacs and 7 gestational sacs,and the implantation rate was 20.89% and17.5%,respectively.But the difference was not statistically significant?P=0.611?.The number of abortion cycles was 22 cycles and 2 cycles,respectively.The abortion rates were 25.29% and 28.57% respectively,and there was no significant difference between the two groups?P=1.00?.5 Analysis of pregnancy outcomes by using ovulation promoting drugs According to the COH scheme,they were divided into four groups.Group 1 was GnRH-a long protocol group,group 2 was GnRH-a antagonist protocol group,group 3 was micro-stimulation protocol group,and group4 was GnRH-a short protocol group.The mean female age were 33.69±5.28 years old?38.15±4.88 years old?38.01±4.87 years old and 37.13±5.08 years old.The number of oocytes were 6.57±3.60?3.59±2.72?2.34± 1.81 and 3.74±2.27.There were significant differences at the mean female age and the number of oocytes in the four groups?P<0.01?.There was no difference between the four groups at the average number of transplant embryos?P>0.05?.The clinical pregnancy rates of the four groups were52.03%?group 1?,25.39%?group 2?,16.67%?group 3?and 33.33%?group 4?respectively.The pregnancy rate of GnRH-a long protocol group was higher than antagonist protocol group and micro-stimulation protocol group?P<0.05?.The implantation rate were 38.89%?group 1?,17.44%?group 2?,12.12%?group 3?and17.54%?group 4?respectively.The GnRH-a long protocol group was higher than the other groups.There was no difference between the other groups?P>0.05?.The miscarriage rate were 32%?group 1?,24.49%?group 2?,33.33%?group 3?and 10%?group 4?respectively.There was no statistical significance?P>0.05?.The clinical pregnancy rate,implantation rate and abortion rate were compared between thepatients of under the age of 35 years old among the group 1 and group 2.The clinical pregnancy rates of long protocol group and antagonist group were 55.88%and 42.59%.The implantation rates were 46.03% and 30.43%.The abortion rates were 21.05% and 4.34%.Statistical analysis showed no difference?P>0.05?among them.Conclusions:1.The body mass index of the patients with poor ovarian response showed an increasing trend with age.2.Patients with poor ovarian response should prefer to use drugs firstly to increase the number of oocytes and the number of embryos available for transplantation.3.There was no significant difference in clinical pregnancy rate,implantation rate and abortion rate between the long-term regimen and the GnRH antagonist regimen.Background People have tried various methods to help patients with low ovarian response,and the antagonist protocol is a common method in clinical application in recent years.Because the antagonist is only used in the second half of the follicle to inhibit the body LH peak,the antagonist program has the advantages of short medication time and low cost.The study showed that ovarian can also promote ovulation in the luteal phase recently.Many scholars have proved that the oocytes obtained during luteal phase can be developed into high quality embryos in vitro.The Luteal-phase ovarian stimulation protocol which was applied to patients of normal ovarian function achieved a higher pregnancy rate.This investigation was a retrospective study to compare the effect of the Luteal-phase ovarian stimulation protocol with gonadotropin-releasing hormone antagonist protocol in women with poor ovarian response.Clinical information1Object of study The data for this study were retrieved from patienfs medical records from January 2012 to June 2016.Four hundred and seventy-two cycles of four hundred thirteen were enrolled from our computerized IVF database.We selected patients according to the European Society of human reproduction and embryology.The inclusion and exclusion criteria are the same as the first part.2Grouping criteria According to the COH scheme,they were divided into two groups: group LP?luteal-phase ovarian stimulation protocol?and group AN?gonadotropin releasing hormone antagonist protocol?.In group LP,we began to use ovulation inducing drugs within 2 days after ovulation or oocytes retrieval.The highest quality embryos were cryopreserved for later transfer.The endometrium preparation of thawed embryo transfer was a natural or artificial cycle.The pregnancy outcome of the first thawed embryo transfer was selected and compm*ed.In group AN,we began to use ovulation inducing drugs on day 2 of the menstrual cycle.When the leading follicle exceeded 13 mm indiameter,GnRH antagonist was started daily until the day of HCG administration.The highest quality embryos were transferred.3 Statistical methods The statistical methods are the same as the first part.Results From January 2012 to June 2016,413 women with poor ovarian responses had been chosen.108 patients carried out the Luteal-phase ovarian stimulation protocol.305 patients carried out the GnRH antagonist protocol.The mean female age were 37.31 ±5.12 years old and 38.15±4.88 years old.The mean body mass index were 23.74±2.90 kg/m2 and 24.38±3.10 kg/m2.The base FSH values are 10.97±423 mlU/mL and 10.23±3,36 mIU/mL.There was no statistical significance?P>0.05?.The total days of hMG used were 9.91 ±2.30 days and 8.83±2.11 days.The total dosage of hMG used were 2088.22±561.30 IU and 1699.43±668.10 RJ.The total days and dosage of hMG used in LP protocol Group were higher than that of the AN protocol Group?P<0.01?.The Estradiol level were 832.54±675.50pg/ml and1057.35±889.91 pg/ml.The Estradiol?E2?level on the day of HCG administration in Group LP was significantly lower than that of the Group AN?P<0.05?.The average number of oocytes retrieved in the LP and AN protocol Group was3.53±2.51,3.59±2.72 respectively.The average number of embryos transferred were 1.72± 1.21 and 1.78±0.60.There was no statistical significance?P>0.05?.The clinical pregnancy rate and implantation rate in the LP and AN protocol were26.19%?22/84?,25.39%?49/193?,and 15.48%?24/155?,17.44%?60/344?respectively.The miscarriage rate in the LP and AN protocol were 22.72%?5/22 LP group?and 24.49%?12/49 AN group?.There was no significant difference in pregnancy rate,implantation rate and abortion rate between the two groups ?P>0.05?.Conclusions The protocol of luteal phase ovarian stimulation can be applied to women with poor ovarian response,with the same clinical pregnancy rate and implantation rate compare with GnRH antagonist protocol. |
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