The causes of high-order multiple gestation

Most recent reviews of multiple gestations have reported that the major cause of triplet and quadruplet pregnancy is therapy with human menopausal gonadotropin (hMG). In an attempt to decrease the number of high-order multiple gestations due to hMG, serial ovarian ultrasound evaluation was introduced in the mid-1970s. To assess the impact of changing technology on the causes of high-order multiple gestation, we reviewed the experience at our institution from 1983 to 1987. During this time period, 35,119 deliveries were performed, including 13 triplet and 2 quadruplet deliveries. Of the triplet and quadruplet pregnancies, 3 (20%) patients conceived spontaneously, 11 (73%) conceived in association with ovulation induction, and 1 (7%) conceived during an IVF cycle. Of the pregnancies associated with ovulation induction, 9 (82%) were associated with clomiphene therapy and only 2 (18%) with hMG therapy. Of the clomiphene patients, 6 (67%) conceived at a dose of 50 mg per day for five days and 5 (55%) conceived during the first cycle. At the present time, in our institution, hMG therapy is no longer the major cause of triplet and quadruplet pregnancies. It is possible that serial serum estradiol and ovarian ultrasound monitoring of hMG cycles has contributed to the low number of hMG-induced triplet and quadruplet pregnancies that we observed.     

Clinical experience in the induction of ovulation and pregnancy with pulsatile subcutaneous administration of human menopausal gonadotropin: a low incidence of multiple pregnancy

The pulsatile subcutaneous administration of human menopausal gonadotropin (hMG) or follicle-stimulating hormone (FSH) was used for induction of ovulation in 26 patients with hypothalamic/pituitary amenorrhea or polycystic ovary syndrome (PCO). Ovulation was observed in 116 (90.6%) of 128 treatment cycles, and 15 (16 treatment cycles) of 26 patients became pregnant. All 14 fetuses, excluding two pregnancies interrupted spontaneously at weeks 6 and 9, were singleton conceptions. Ovarian hyperstimulation was observed in 15.6% of treatment cycles. Five patients with PCO who failed to conceive on the hMG regimen also received pulsatile FSH administration. Although ovulation rates in PCO patients did not differ significantly between the hMG (88.1%) and FSH (88.2%) regimens, a significant reduction in the average dose of FSH (P less than 0.05) was observed with pulsatile FSH administration. Furthermore, the number of patients who conceived during the FSH regimen was significantly greater than that found with hMG treatment. The present data demonstrate that pulsatile subcutaneous administration of hMG or FSH is effective in induction of successful ovulation and establishment of singleton pregnancy in patients with various types of anovulatory infertility.     

促排卵治疗对多囊卵巢综合征患者子宫内膜整合素αv,β3表？…

目的 了解促排卵药物对多囊卵巢综合征（ＰＣＯＳ）患者黄体中期子宫内膜整合素αｖ、β３表达的影响。方法 应用单克隆抗体,采用免疫组织化学技术对２２例正常妇女、４０例无排卵ＰＣＯＳ患者促排卵治疗后黄体中期的子宫内膜整合素αｖ、β３进行测定。结果正常妇女子宫内膜整合素αｖ、β３表达在“着床窗口期”呈现强阳性;而氯米芬（ＣＣ）及绝经期促性腺激素（ｈＭＧ）抑制αｖ、βｂ的表达,使其表达呈弱阳性;而促性腺素释     

不同促排卵方案来源胚胎冻融胚胎移植妊娠结局分析北大核心CSCD

目的探讨不同促排卵方案来源胚胎冻融胚胎移植(FET)的妊娠结局。方法回顾性分析2016年1月至2021年5月在南通大学附属医院生殖医学中心接受体外受精或卵泡浆内单精子注射-胚胎移植(IVF/ICSI-ET)治疗,因鲜胚移植失败或全胚冷冻而要求FET的252个周期,根据刺激周期方案的不同将其分为5组:高孕激素促排卵(PPOS)组(n=26)、枸橼酸氯米芬+人绝经期促性腺激素(CC+hMG)组(n=50)、超短方案组(n=57)、拮抗剂组(n=78)及长方案组(n=41),分析各组的临床结局。结果 252个FET周期中,各组体重指数(BMI)、不孕年限、不孕类型、刺激周期时扳机日E2水平/扳机日直径≥14mm卵泡数、移植周期时转化日内膜厚度、转化日E2水平、移植D3胚胎或囊胚比例,差别均无统计学意义(P>0.05)。各组间患者年龄、基础FSH、获卵数、刺激周期Gn总量及平均移植胚胎数,差异有统计学意义(P<0.05)。各组间hCG阳性率、临床妊娠率、流产率及继续妊娠率差异无统计学意义(P>0.05)。但CC+hMG组hCG阳性率、临床妊娠率及继续妊娠率数值上最低,长方案组hCG阳性率、临床妊娠率及继续妊娠率数值上均最高。多因素logistic回归分析发现CC+hMG组FET临床妊娠率低于长方案组,差别有统计学意义(P<0.05),但与其他各组比较差异无统计学意义。其他4组间比较妊娠结局无明显差异(P>0.05)。结论 PPOS、超短方案、长方案、拮抗剂促排卵方案来源胚胎FET妊娠结局在数值上优于CC+hMG促排卵方案,其中长方案显著优于CC+hMG促排卵方案。     

A comparison of clinical and laboratory methods in monitoring human menopausal gonadotropin therapy

Twenty infertile, anovulatory women were treated with human menopausal gonadotropin (hMG) for a total of 61 treatment cycles. Cervical scores (all cycles) and vaginal maturation indices (23 cycles) were compared with serum concentrations of total immunoreactive estrogens to determine their clinical efficacy in monitoring hMG treatment. All courses of therapy were judged to have induced ovulation. Singleton pregnancies occurred in nine patients, and one patient conceived twice. All pregnancies were uncomplicated. There was good clinical correlation between cervical score and increasing estrogen levels in approximately one-third of the cycles. Most of these good correlations occurred in patients with low estrogen status. Very poor correlation was found with vaginal cytologic changes. Therefore, in conjunction with serum estrogen determinations, the cervical score is a safe and less expensive means of monitoring hMG therapy in selected patients.     

Influence of weight in the induction of ovulation with human menopausal gonadotropin and human chorionic gonadotropin

Patients failing to ovulate and conceive on clomiphene citrate (CC) or CC plus human chorionic gonadotropin (hCG) or patients with pituitary gonadotropin deficiency are candidates for human menopausal gonadotropin (hMG) plus hCG therapy. The duration and number of ampules needed to stimulate ovarian response leading to ovulation and/or pregnancy vary individually. Seventy-one patients who had complete follow-up evaluation and accurately documented body weights at the time of therapy were considered for the study. Of these 71 patients, 41 (57.3%) conceived in 293 cycles. The average number of ampules of hMG used by patients with 10% to 20% below ideal body weight (IBW) was 13.9 +/- 6.3 (mean +/- standard deviation [SD]). The average number of ampules used by patients with normal +/- 10% IBW was 14.2 +/- 3.5. Patients who were overweight by 10% to 25% used 15.3 +/- 5.4 ampules, and patients overweight by greater than or equal to 25% used 20.9 +/- 5.6 ampules of hMG. Eleven patients with severe hypothalamic chronic anovulation needed an average of 20.6 +/- 6.2 ampules. The data reveal a direct relationship between IBW and the amount of hMG needed to induce ovulation and/or pregnancy; however, in the presence of chronic hypoestrogenic conditions, it is expected that these patients will need higher amounts of hMG, regardless of body weight.     

Risk of multiple gestation after ovulation induction in polycystic ovary syndrome

OBJECTIVE: To compare the incidence of multiple gestation following treatment with clomiphene citrate (CC), metformin (MET) or gonadotropins in polycystic ovary syndrome (PCOS) patients undergoing ovulation induction. STUDY DESIGN: This was a retrospective, cohort study performed in an academic reproductive endocrine practice. PCOS patients presenting for first-trimester ultrasound were identified and assigned to 1 of 3 groups: CC-resistant patients who conceived after use of metformin +/- CC (group A), CC-resistant patients who conceived after gonadotropins (group B) and PCOS patients who conceived with CC only (group C). Multiple pregnancy outcome data were collected by chart review and patient interview. RESULTS: One hundred one pregnancies were identified in PCOS patients who had conceived after ovulation induction (OI). The rate of multiple gestation was higher in group B (36%) than in A (0%) or C (11%). CONCLUSION: The rate of multiple births was significantly lower with MET use during OI. Because multiple gestation is associated with higher complication rates and medical costs, our data offer an additional reason for use of MET for OI in PCOS patients who fail CC.     

Plasma estrogen monitoring of ovulation induction.

Eight hMG-hCG therapy cycles in 6 anovulatory infertile patients are presented. Daily plasma estrogen monitoring during the therapy contributed to success in inducing ovulation in all 6, 3 of whom established pregnancies and delivered healthy babies. The duration of hMG therapy required varies among individuals. Duration and dosage can be determined on the basis of daily plasma estrogen levels. Administration hCG is recommended to trigger ovulation when these levels reach 300 to 600 pg/ml. Although success in ovulation induction and pregnancy is achievable, multiple ovulation and multiple pregnancy cannot be predicted or prevented.     

Extension of the clomiphene citrate stair-step protocol to gonadotropin treatment in women with clomiphene resistant polycystic ovarian syndrome

Our objective was to evaluate the safety and efficacy of direct initiation of gonadotropin ovarian stimulation without prior withdrawal bleeding in anovulatory clomiphene citrate (CC) resistant polycystic ovarian syndrome (PCOS) patients. Eighteen PCOS patients underwent ovulation induction with CC using a stair-step regimen. Patients who failed to respond to the maximal dose of CC initiated gonadotropin stimulation without inducing withdrawal bleeding, using the chronic low dose regimen. The primary outcome measure was the time to ovulation from the beginning of CC treatment until the day of ovulatory trigger. This was compared with the time to ovulation calculated according to the traditional approach, which includes inducing progesterone withdrawal bleeding between each CC dose increment and before gonadotropin therapy. The time to ovulation in the study group was 67.0?±?6.8 days. The estimated time to ovulation according to the traditional approach was approximately 110 days. The clinical pregnancy rate was 44% (8/18), and all pregnancies were singletons. One patient miscarried; hence the live birth rate was 38.9% (7/18). Direct initiation of gonadotropin therapy without prior induction of withdrawal bleeding in clomiphene resistant PCOS patients results in considerable reduction of the time to ovulation and is both safe and efficacious.     

Ovulation induction increases serum levels of insulin-like growth factor binding protein 1.

The effect of ovulation induction on serum insulin-like growth factor binding protein 1 (IGFBP-1) level in relation to sex hormone binding globulin (SHBG) levels was evaluated. Serum samples were collected 8 to 12 days after ovulation from 26 women undergoing ovulation induction with clomiphene citrate (CC), and from 58 women treated with CC in combination with human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG). In addition, serum samples were obtained from 63 spontaneously ovulating women and from 12 women during an anovulatory cycle. Luteal phase serum IGFBP-1 levels were 4.22 +/- 2.95 micrograms/L (P less than .05) in the CC group and 7.31 +/- 6.13 micrograms/L (P less than .001) in the CC/hMG/hCG group as compared to unstimulated ovulatory cycles (2.64 +/- 2.52 micrograms/L). No significant difference in IGFBP-1 levels was seen between spontaneously ovulatory and anovulatory cycles. The serum IGFBP-1 levels correlated positively to SHBG levels (r = .52, P less than .001). The data show that ovulation induction increases serum IGFBP-1 levels in parallel to SHBG levels, indicating that ovarian stimulation, which results in increased steroid hormone production, also induces changes in other factors known to modulate steroid hormone actions.     

The importance of human chorionic gonadotropin support of the corpus luteum during human gonadotropin therapy in women with anovulatory infertility

One hundred ten women with anovulatory infertility (World Health Organization [WHO] group I n = 50, WHO group II n = 60) were given 341 treatment courses with human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG). Additional hCG was given as single or repeated injections during the luteal phase in 205 ovulatory cycles. In WHO group I, the incidence of luteal phase defects was lower and the pregnancy rate higher in cycles with extra hCG administration during the luteal phase than in cycles with no extra hCG. In WHO group II, there was no such difference after supplemental hCG. The abortion rate was the same after cycles with or without extra hCG administration. It is suggested that during ovulation induction with hMG/hCG in anovulatory women with no evidence of endogenous estrogen activity, the luteal phase should be supplemented with additional hCG.     

Sonography of the endometrium during conception and nonconception cycles of in vitro fertilization and embryo transfer

The thickness of the endometrium was compared in 15 patients who conceived and 15 who did not with an in vitro fertilization and embryo transfer (IVF-ET) protocol after ovulation induction with human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG). There was no statistically significant difference (P = 1.0) in the endometrial thickness in the conception versus the nonconception group. Average estradiol (E2) values and number of mature follicles were also not statistically different in the two groups (P = 0.78, P = 0.81). There was a slightly significant difference in the number of embryos transferred in the conception versus nonconception groups (2.5 versus 1.9, P = 0.005). However, the most significant difference between the conception and nonconception groups was the total number of oocytes retrieved (4.4 versus 2.8, P = 0.005). These findings indicate that there are no sonographically detectable differences in the endometrial thickness in patients who achieve pregnancy versus those that do not when given a similar ovulation induction regimen of hMG/hCG for IVF-ET.     

Ovulation monitored by serum 17 beta-estradiol and ultrasound: differential ovarian response to human gonadotropins in various anovulatory states

Ovulation induction with human gonadotropins (hMG or pFSH and hCG) was simultaneously monitored with daily serum 17 beta-estradiol measurements and ultrasound in 38 infertile women. They were subgrouped as follows: A, hypogonadotropic hypogonadism (n. 7); B, polycystic ovary syndrome (n. 13); C, non-PCO chronic anovulation (n. 6); D, unexplained infertility (n. 12). The dose of hMG and the duration of therapy were assessed individually depending on the results of the monitoring when serum estradiol concentration was 500-1500 pg/ml and/or ultrasound showed of a follicle of at least 18 mm, hMG was stopped and hCG was administered 36 hours later. Ovulation was obtained in 61 cases and pregnancy occurred in 12 women out of 64 monitored cycles. The highest pregnancy rate was observed in hypogonadotropic hypogonadism; this group also required the greatest total dose of hMG to obtain ovulation. We confirm that women with PCOS are at increased risk with this therapy, since 5 subjects in our series showed signs of ovarian hyperstimulation in spite of the lowest total dose of FSH administered to this group. We conclude that anovulatory states of various origin are associated with different ovarian sensitivity.     

Avoidance of cancellation of potential hyperstimulation cycles by conversion to in vitro fertilization-embryo transfer

OBJECTIVE: The study was undertaken to minimize the rate of ovarian hyperstimulation and to avoid cancellation of human treatment cycles in women treated with human menopausal gonadotropin (hMG) for induction of ovulation. SETTING: Patients were treated in the fertility clinic and in vitro fertilization unit of our institution, which is a government, university-affiliated hospital. PATIENTS: Ninety anovulatory patients were treated with hMG. Of these, 12 were at high risk for ovarian hyperstimulation. The criteria for potential ovarian hyperstimulation syndrome were rising excessive 17 beta-estradiol levels of greater than 1,500 pg/mL in the presence of multiple follicles with a mean diameter greater than 15 mm. These patients were transferred for continuation of treatment to our in vitro fertilization-embryo transfer (IVF-ET) unit. INTERVENTIONS: The patients underwent ova retrieval by the ultrasonically guided transvaginal approach. RESULTS: Of the 12 patients, 5 conceived (41.6%). Two patients had a mild ovarian hyperstimulation syndrome, and 1 had a moderate syndrome and was hospitalized for observation for 48 hours. CONCLUSION: In view of the results, we suggest that IVF-ET should be considered in cases in which ovarian hyperstimulation syndrome is imminent, rather than withhold human chorionic gonadotropin and cancelling the treatment cycle.     

Effect of ultrasound monitoring of follicular growth on the conception rate. A clinical study

Periovulatory ultrasonography (POUS) was performed on 59 anovulatory women over 523 treatment cycles. Follicular development was stimulated with either clomiphene citrate (CC) or human menopausal gonadotropin (hMG). Thirty-one pregnancies were induced; 23 went to term. Three factors were considered in evaluating the incidence of conception: the patient's age, drug use and the presence or absence of POUS. There was no evidence that the pregnancy rate after POUS differed from that without it (estimated conception rate ratio = 1.2:1, P = .76). Similarly, conceptus viability was not demonstrably different whether POUS was used or not (P = 1.00). However, the data show a strong advantage of hMG over CC in achieving conception (estimated conception rate ratio = 5.85, P less than .0001) and no disadvantage in conceptus viability (P = 1.00). The data also suggest that in women less than 30 years of age with polycystic ovaries, ovulation induction is easier to achieve and the conception rate higher than in older women. There was no evidence that POUS decreased the conception rate or increased fetal wastage.     

Comparative trial of luteinizing hormone-releasing hormone analog/human menopausal gonadotropin and clomiphene citrate/human menopausal gonadotropin in an assisted conception program

To establish the usefulness of a new drug regimen in an assisted conception program, a trial was performed comparing clomiphene citrate (CC) plus human menopausal gonadotropins (hMG) with a new regimen of intranasal luteinizing hormone-releasing hormone (LH-RH) analog plus hMG. One hundred two patient cycles received treatment with CC and hMG and 118 patient cycles received treatment with LH-RH analog and hMG. Fifteen percent of cycles were canceled in the CC group and 8% in the analog group. Four percent of cycles in the CC group were canceled due to premature ovulation. The number of oocytes collected in the analog group was significantly higher than in the CC group (8.5 versus 5.5), as was the number of mature oocytes (3.5 versus 2.7). However, the percentage of mature oocytes was higher in the CC group (54.2% versus 42.3%). The number of embryos resulting from in vitro fertilization as well as the number of cleaving embryos were significantly higher in the analog group (5.2 versus 2.8 and 4.6 versus 2.3, respectively). The pregnancy rate in the analog group was significantly higher than in the CC group (30.6% versus 16.1%), as was the live birth rate (21% versus 8%). Early pregnancy loss was significantly higher in the CC group than in the analog group (35% versus 9%); and the serum level of LH on the day of human chorionic gonadotropin (hCG) administration was also significantly elevated in the CC group when compared with the analog group (8.1 versus 4.1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Alternate regimens for ovulation induction in polycystic ovarian disease

The patient with PCOD remains a challenge to the reproductive endocrinologist. Although successful induction of ovulation can often be achieved using standard therapeutic regimens of CC or hMG, too often this group of anovulatory patients fails to respond as expected. Over the past 10 to 15 years, alternate approaches to ovulation induction have been investigated with encouraging results. Whereas no one method is productive in all patients, these varied regimens offer us a number of options in dealing with this difficult clinical problem.     

Comparison of clomiphene citrate and letrozole for ovulation induction in women with polycystic ovary syndrome: a prospective randomized trial

To compare the therapeutic efficacy of clomiphene citrate (CC) and letrozole (LE) on ovulation, pregnancy, and live birth in women with polycystic ovary syndrome (PCOS); and to ensure if LE can replace CC as the first-line therapy for ovulation induction in these women. This is a prospectively, randomized, controlled trial in the tertiary hospital. Two-hundred and sixty-eight anovulatory PCOS patients were treated by CC or CC plus metformin and LE or LE plus metformin for three continuous cycles or conception; their ovulation rates, pregnancy rates, and live birth rates were calculated and compared. No significant difference was noted among the four groups regarding to the baseline data of clinical manifestations, serum sex hormone levels, and serum insulin levels. A total of 240 patients completed the therapies. The ovulation rate was significantly higher in the group LE than the group CC; however, no significant difference was noted between the groups LE and CC, CC, and CC?+?MET, or LE and LE?+?MET in the pregnancy rate, abortion rate, and live birth rate. No birth defect was found in the total of 63 newborns. CC regimen was still recommended to be the first-line therapy of ovulation induction for PCOS.     

Short-term luteinizing hormone-releasing hormone agonist treatment: prospective trial of a novel ovarian stimulation regimen for in vitro fertilization

Over a period of 4 months, 262 infertile couples participated in a prospective pseudorandom trial of a novel short-term luteinizing hormone-releasing hormone/human menopausal gonadotropin (LH-RH/hMG) treatment; the short-Buserelin-gonadotropin (Hoechst, Hounslow, United Kingdom) regimen. Patients treated with the short-Buserelin-gonadotropin regimen had a significantly higher likelihood of achieving pregnancy than patients treated with the standard clomiphene citrate (CC)/hMG regimen (respectively, 35.5% and 18% per treatment cycle). A significantly higher number of eggs were collected after short-Buserelin-gonadotropin treatment than CC/hMG, but the proportion of patients having a given number of embryos replaced was similar in the two groups. The short-Buserelin-gonadotropin-treated patients were distinguished from the CC/hMG-treated group by significantly lower levels of LH in the late follicular phase and a lower plasma level of estradiol. A detrimental relationship between elevated endogenous LH secretion and failure of implantation has been established. The nature of the short-Buserelin-gonadotropin regimen provokes high levels of endogenous gonadotropin secretion in the early follicular phase and induces a suppression of gonadotropin secretion in the late follicular phase. This may be the physiologic basis of the greater implantation rate after short-Buserelin-gonadotropin treatment than is seen with conventional CC/hMG treatment.     

A comparative, randomized study of low-dose human menopausal gonadotropin and follicle-stimulating hormone in women with polycystic ovarian syndrome

Treatment with low-dose follicle-stimulating hormone (FSH) is associated with a high rate of ovulation in anovulatory women with polycystic ovarian syndrome (PCOS), but it is not clear whether the success of treatment is because of the use of pure FSH or the low dose of gonadotropin. We undertook a randomized controlled study to compare the effects of urinary FSH and human menopausal gonadotropin (hMG) using a low-dose regimen in 30 women with PCOS. Each subject received a maximum of three cycles of either FSH or hMG. Ovulation occurred in 75% of subjects and in 77% of cycles induced with FSH and in 94% of women, 85% of cycles of those treated with hMG. A single dominant follicle developed in 70% (FSH) and 65% (hMG) of cycles, respectively. Five singleton pregnancies occurred in each group. This study shows that low-dose FSH and hMG are equally successful in inducing ovulation, suggesting that the success of treatment depends on the low dose of gonadotropin used rather than the presence or absence of luteinizing hormone in the preparation.