The periovulatory and luteal phase of conception cycles following in vitro fertilization and embryo transfer

The pattern of periovulatory and luteal phase levels of serum estradiol (E2) and progesterone (P) were compared between 8 conception and 28 nonconception cycles of patients undergoing in vitro fertilization (IVF). Ten additional women served as control subjects and did not undergo follicular aspiration. Follicle growth was induced with an individualized Pergonal (human menopausal gonadotropin) regimen, and laparoscopy was performed 36 hours after human chorionic gonadotropin administration. The length of the luteal phase did not differ significantly among the three groups and was between 14 and 15 days in duration. When IVF conception cycles were compared with nonconception cycles, although no difference in the number of large follicles was observed (4.25 +/- 0.45 versus 3.6 +/- 0.25), the patterns of E2 and P differed significantly. Daily serum E2 levels tended to be higher in the periovulatory phase in conception cycles when compared with nonconception cycles, and were significantly (P less than 0.05) higher in the early, mid, and late luteal phases. Serum P levels were significantly higher (P less than 0.05) in conception cycles from the midluteal phase onward. A decline in both serum E2 and P in the midluteal phase in conception cycles suggested some degree of corpus luteum deficiency. It is suggested that high E2 levels in the periovulatory phase may be an indicator of better follicular development under human menopausal gonadotropin stimulation and that the deficiency observed in the late luteal phase is overcome with the establishment of pregnancy.     

Human chorionic gonadotropin, estradiol, and progesterone profiles in conception and nonconception cycles in an in vitro fertilization program

In 22 consecutive in vitro fertilization cycles stimulated with purified follicle-stimulating hormone, human chorionic gonadotropin (hCG), estradiol (E2), and progesterone (P) were measured every 3 days during the luteal phase. All serum measurements were normalized to the day of hCG administration (day 0). There was a total of nine pregnancies; two were biochemical pregnancies, whereas 7 of the 22 women had clinical pregnancies (31.8%). Of these, two miscarried and five had term pregnancies (three singleton, two twin). Conception cycles could be differentiated from nonconception cycles by serum E2 levels on day 8 (P = 0.035), by hCG levels on day 11 (P = 0.03), and by P levels on day 14 (P = 0.001). From days 8 to 11, hCG levels plateaued in conception cycles and decreased in nonconception cycles. However, during that period, E2 and P fell in both groups of women. This decline in sex steroids, which was observed in both conception and nonconception cycles, may well negatively influence endometrial development during the peri-implantation period and compromise conception, resulting in failure to conceive, biochemical pregnancy, and early miscarriage.     

Salivary progesterone as an index of the luteal function

Salivary progesterone (SP) is proposed as a useful index for estimation of luteal function. In 32 normal luteal phases with in-phase endometrial biopsies, the luteal SP assayed three times between 11 and 4 days before menses correlated significantly with the matched plasma P (PP) values and the ratio of SP to PP X 100 = 1.02. In 19 disharmonic luteal phases, a syndrome characterized by retarded endometrial development and apparently normal corpus luteum function, SP and PP were both in the normal range. In five conception cycles, SP and PP correlated significantly and increased during the evolution of the corpus luteum of pregnancy. In four cycles of luteal insufficiency, P concentrations were lower than normal in saliva as well as in plasma.     

Salivary estradiol and progesterone levels in conception and nonconception cycles in women: evaluation of a new assay for salivary estradiol

OBJECTIVE: To determine the usefulness of salivary E2 and progesterone for noninvasive assessment of ovarian function. DESIGN: Prospective study of salivary hormone levels in women planning a pregnancy. SETTING: Department of Obstetrics and Gynecology at Northwestern University Medical School in Chicago, Illinois. PATIENT(S): Fourteen women aged 23-39 years with regular menstrual cycles who were planning a pregnancy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Salivary estradiol and progesterone concentrations. RESULT(S): The sensitivity of the E2 assay is 2.0 pmol/L; the interassay coefficient of variation was 5.2% (mean value 17 pmol/L). Recovery of E2 added to saliva was 106%. The correlation with simultaneous serum samples was 0.71. Menstrual cycle patterns contained a preovulatory depression and a midcycle surge. By comparison with nonconception cycles, the luteal phases of conception cycles had significantly elevated salivary E2 within the first 5 days after ovulation. Salivary progesterone was significantly elevated but not until 10 days after ovulation. CONCLUSION(S): Salivary measurements of E2 and progesterone can be used as noninvasive methods for assessment of ovarian function. Salivary specimens can be collected at home and brought to the laboratory for analysis, obviating the need for frequent phlebotomy. The sensitivity and precision of the salivary E2 assay make it comparable with assays of serum E2 for assessing changes in hormone levels.     

Endometrial dating in the conception cycle.

OBJECTIVE: To investigate endometrial dating during the conception cycle. DESIGN: Endometrial biopsies of the last half of the luteal phase of conception cycles were dated based on urinary luteinizing hormone (LH) surges. SETTING: Endometrial samples were obtained from women attending the fertility clinic of the Department of Obstetrics and Gynecology at Gunma University Hospital. PATIENTS: One hundred eighty-five women, of whom 15 (8.1%) conceived during this study. MAIN OUTCOME MEASURES: Urinary LH surge, serum progesterone (P) levels, and endometrial dating. RESULTS: All 10 women who conceived showed 2 or within 2 days in-phase endometrial biopsies on days 7 to 11 after the LH surge. In 4 of 5 women biopsied on day 12, an unequivocally delay in the stroma was found, i.e., a persistence of edema and poor development of predecidual reaction. Since serum P levels in conception cycles were significantly higher than in nonconception cycles on days 10, 11, and 12, we interpreted this delay in the stroma as a consequence of conception. CONCLUSION: Endometrial specimens during the last half of the luteal phase of conception cycles are in-phase until day 12. On day 12, gestational hyperplasia causes apparent out-of-phase.     

Luteal rescue in in vitro fertilization-embryo transfer

The luteal phase hormone profiles of two groups participating in the Yale in vitro fertilization (IVF) program were compared. A control group (group I) consisted of 28 women (28 cycles) who received our standard ovulation induction regimen (no luteal phase support). The treatment group (group II) consisted of 40 women (42 cycles) who were prospectively studied after receiving luteal phase support with 10,000 IU human chorionic gonadotropin (hCG) 5 days after the initial hCG dose. The groups were matched for age and cause of infertility. Estradiol (E2) and progesterone (P) were measured on the day of embryo transfer and every 3 to 4 days thereafter. Luteal phase hCG support significantly augmented (1) E2 and P levels in the conception cycles of group II compared with group I and (2) P levels in the nonconception cycles of group II compared with group I. The midluteal decline in E2 and P that was observed in group I was minimized or prevented in group II. An ongoing pregnancy rate of 19% was achieved in group II. This was not statistically different from the 13% ongoing pregnancy rate noted in a separate group of 163 tubal factor couples undergoing IVF after our standard ovulation induction regimen during the period of the study. In summary, the luteal phase hormone profiles of IVF cycles were improved by supplementation with hCG. It is concluded that this type of intervention may serve to rescue potentially failing corpora lutea and thereby optimize the peri-implantation hormonal milieu.     

Changes in uterine and ovarian arterial impedance during the periovulatory period in conception and nonconception cycles

OBJECTIVE: To evaluate whether the Doppler velocimetry of uterine and ovarian arteries during the periovulatory period in conception cycles differs from that in nonconception cycles. DESIGN: Transvaginal color Doppler sonography was used to assess uterine and ovarian perfusion in 63 infertile women during the periovulatory period. RESULTS: In the conception cycles (n = 16), the PI values of uterine arteries at the day of ovulation were significantly less than those in nonconception cycles (n = 47). There were no significant differences in the PI values of ovarian arteries between the conception and nonconception cycles. CONCLUSIONS: In the present study, the conception cycles showed lower vascular impedance in the uterine during the periovulatory period than did the nonconception cycles. This endometrial perfusion presents an accurate noninvasive assay of uterine receptivity that can be used to predict the successful outcome of implantation and to reveal unexplained infertility problems.     

The luteal phase in polycystic ovary syndrome during ovulation induction with human menopausal gonadotropin with and without leuprolide acetate

Little data exist on the effects of adjunctive therapy with leuprolide acetate (LA) in the luteal phase of women with polycystic ovary syndrome (PCOS) undergoing ovulation induction with human menopausal gonadotropin (hMG). Additionally, it is not known whether gonadal steroid concentrations in the luteal phase of induced cycles in PCOS are predictive of pregnancy. In this prospective, randomized study comparing cycles using hMG alone (n = 26) with cycles using hMG with LA (n = 33), no differences were noted between treatment groups in progesterone (P), estradiol (E2), and P:E2 ratios on luteal days 3, 6, and 9. When all treatment cycles were pooled, there were no differences in P, E2, or P:E2 ratios, comparing conception and nonconception cycles. We conclude that adjunctive therapy with LA in PCOS patients undergoing ovulation induction with hMG does not alter the luteal phase concentrations of P, E2, and P:E2. Furthermore, no correlation was found between the serum concentrations of these luteal phase steroids and cycle fecundity.     

Elevation of serum progesterone with oral micronized progesterone after in vitro fertilization. A randomized, controlled trial

In a randomized, controlled trial, oral micronized progesterone (P4) supplementation effectively elevated luteal phase serum P4 levels after in vitro fertilization (IVF). Of 34 nonconception IVF cycles, 12 were supplemented with oral micronized P4, 200 mg four times daily, beginning the day of oocyte retrieval, while 22 control cycles did not receive supplementation. With oral micronized P4 supplementation the P4 levels were higher (P less than .001) and the luteal phase longer (P less than .05). Oral micronized P4 supplementation appears to be a convenient method of supporting serum P4 levels during the luteal phase after IVF.     

Effects of prolactin and bromocriptine on the luteal phase in infertile women

Infertile women with regular periods but with shortened luteal phases were found to have higher mean levels of serum prolactin and lower serum progesterone levels in the midluteal phase than women with apparently normal ovarian function (P less than 0.001). Serum estrogens and gonadotropins did not differ from the reference group but the ratio FSH/LH was reduced in the midluteal phase (P less than 0.05). LHRH-loading test in the midfollicular phase also resulted in a lower ratio of FSH/LH (P less than 0.05). Thirty-six infertile women with short luteal phases were treated with bromocriptine in a double-blind fashion. The drug moderately reduced the length of the cycle (P less than 0.01). The hyperthermia of the luteal phase was measured planimetrically. Both the total area and the area per day of the luteal phase were significantly increased during the cycles of active treatment (P less than 0.02 and 0.05, respectively). Prolactin was depressed by the drug. After cessation of therapy a very significant rebound elevation of prolactin for at least 2 wk was noted. Bromocriptine therapy further reduced FSH levels at midcycle. Estrogens were elevated during the midluteal phase whereas progesterone was not affected by the treatment. Seven conceptions occurred during the study, six of which during placebo treatment. The conception cycles were characterized by significantly higher levels of progesterone and estrogens during the luteal phase as opposed to the infertile cycles. Four of the pregnancies terminated in spontaneous abortion. The endocrine data of these conception cycles did not differ from those of the successful ones.     

月经周期中唾液和血清孕酮及雌二醇的浓度变化

本文采用~(125)碘标记放射免疫方法,以固相二抗作为分离系统,不经 萃取,直接快速测定唾液中孕酮及雌二醇的浓度。连续每日观察10名育龄妇女正常月经周期中唾液和血清中孕酮及雌二醇的水平变化。滤泡期、排卵期及黄体中期的唾液中孕酮浓度分别为57.7±11,69.3±10及364±33pmol/L(G.M±S.D);雌二醇浓度则分别为1.88±0.6,4.46±0.12及2.56±0.3pmol/L(G.M±S.D)。唾液中激素水平约为血清的0.5～3％,整个月经周期中,唾液和血液的二种甾体激素水平起伏一致,呈平行关系,其相关性显著(r>0.64,p<0.001)。大多数受试者在黄体期夜间(24:00～6:00),唾液的雌二醇水平较高,下午(14:00～16:00)水平较低而平稳。二组间差异显著(P<0.01)。孕酮水平未见明显昼夜变化。唾液孕酮及雌二醇的测定,有标本收集方便的优点,适用于连续测定,可以作为监测卵巢功能及预测排卵的可靠指标。     

Progesterone:estradiol ratios at implantation in ongoing pregnancies, abortions, and nonconception cycles resulting from ovulation induction

The purpose of this study was to compare progesterone (P):estradiol (E2) ratios after ovulation induction at the time of implantation in cycles resulting in ongoing pregnancies or abortions and in nonconception cycles. Material included 43 stimulated conception cycles, 29 with human menopausal gonadotropins (hMG) and human chorionic gonadotropins (hCG), 14 with clomiphene citrate (CC) with or without hCG, and 28 nonconception cycles (13 hMG and hCG, 15 CC with or without hCG). Midluteal P and E2 were measured and expressed in ng/mL. There were no differences in P:E2 ratios (mean +/- SE) for ongoing pregnancies after hMG and hCG (n = 20, 112.6 +/- 14.9), CC and hCG (n = 6, 97.0 +/- 15.9), or CC alone (n = 5, 96.2 +/- 25.5), and the data were pooled. Progesterone:estradiol ratios in 31 ongoing pregnancies and 28 nonconception cycles were 107.0 +/- 10.7 and 115.2 +/- 12.5, respectively, both significantly higher than in 12 abortions (64.5 +/- 13.2). In conclusion: (1) P:E2 ratios at the time of implantation were similar after CC with or without hCG and hMG and hCG treatment; (2) high luteal P:E2 ratio was associated with ongoing pregnancies; and (3) lower P:E2 ratio was seen in cycles leading to spontaneous abortion.     

The frequency of salivary progesterone sampling and the diagnosis of luteal phase insufficiency.

A profile of salivary progesterone concentrations, based on daily samples taken over a full menstrual cycle, provides a detailed picture of changes in luteal function, at the expense of analyzing a large number of samples. Strain can be placed on analytical services by assaying daily samples instead of one or a few serum (or saliva) samples. This study sought to determine the minimum number of salivary progesterone determinations which adequately describe luteal function. Daily salivary progesterone levels from 215 cycles, of which 29 cycles had progesterone profiles indicative of luteal phase insufficiency, were analyzed to ascertain the efficiencies of various sampling patterns of reduced frequency. A single mid-luteal salivary progesterone estimation or the mid-luteal Lenton progesterone index (n = 4) satisfactorily reflected the normal luteal phase, but a frequency of one sample every 3 days over the luteal phase (n = 5-6) was necessary to allow recognition of a short luteal phase or poor progesterone surge.     

Comparative study of serum luteinizing hormone levels in human subjects as measured by radioimmunoassay and radioreceptorassay

A rapid, precise, sensitive, and specific radioreceptorassay (RRA) for serum luteinizing hormone (LH), using a 15,000 X g pellet from bovine corpora lutea, was developed. A comparative study of the serum LH levels in human subjects as measured by this RRA and by radioimmunoassay (RIA) using the same standard preparation was then conducted. The serum LH profile throughout the entire menstrual cycle and the pituitary responsiveness to LH-releasing hormone (LH-RH) stimulation during the two phases of the cycle were studied in two normal women. In addition, LH levels in two normal postpubertal men were measured in blood samples obtained before and after LH-RH administration. Similar, although not identical, LH profiles were found in all cases by both hormone assay methods. Higher RRA-assayable LH values were obtained throughout the menstrual cycle as compared with those obtained by RIA. A significant LH-RH pituitary response in terms of LH in both RRA and RIA during the luteal phase was observed as compared with that observed during the early follicular phase. In the two normal men, the LH values obtained with RRA were higher than those obtained with RIA. It is concluded that the LH RRA is a practical and efficient tool for clinical research.     

Decrease in luteal gonadotropin concentration in conception cycles after in vitro fertilization/gamete intrafallopian transfer

The concentrations of the gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured in the luteal phase of the cycle in patients undergoing ovarian hyperstimulation. In nonconception cycles, FSH and LH were increased in the late luteal phase compared with conception cycles in which both gonadotropins were suppressed. Estradiol (E2) and progesterone concentrations increased in pregnancy cycles and may be the sole cause for the decreased gonadotropin concentrations as shown by equivalent concentrations of LH and FSH in both pregnancy and nonpregnancy cycles after matching for E2 concentrations. Subjects who subsequently had twin pregnancy or a spontaneous abortion were compared with those with a successful ongoing singleton conception. There were no significant differences relative to LH and FSH between the three groups, although in twin pregnancy FSH tended to be lower at day 16 from oocyte recovery. It is concluded that suppression of LH and FSH in hyperstimulated pregnancy cycles occurs after the time of the rising human chorionic gonadotropin concentrations in plasma.     

Luteal hormonal profile of oocyte donors stimulated with a GnRH antagonist compared with natural cycles

The effect of gonadotrophin-releasing hormone (GnRH) antagonist treatment on luteal phase hormonal profile has not yet been fully investigated. Cycle characteristics of 23 fertile donors stimulated with recombinant FSH and the GnRH antagonist, ganirelix 0.25, for IVF and receiving no kind of luteal supplementation were compared with control, natural cycles. Luteal luteinizing hormone (LH) serum concentrations as well area under the curve (AUC) for LH were significantly higher in natural cycles. In addition, luteal phase length was longer in natural cycles compared with donor cycles. Luteinizing hormone values dropped in the luteal phase of the stimulated cycles, with the lowest values being observed in the mid-luteal phase. AUC for progesterone in the luteal phase was significantly higher in the stimulated cycles compared with natural cycles (P < 0.001). Low LH serum concentrations and shortened luteal phase indicate the need for luteal phase supplementation in GnRH antagonist IVF cycles.     

CA-125 levels in human uterine fluid.

OBJECTIVE: To measure uterine fluid CA-125 concentration and to determine if any menstrual cycle phase dependent changes exist in its level. Serum levels are measured for comparison. DESIGN: CA-125 levels in uterine fluid were measured during the follicular and luteal phases of the menstrual cycle. In a sequential study, paired uterine fluid and serum samples were obtained once in both midfollicular and midluteal phases of the same menstrual cycle. RESULTS: CA-125 in uterine fluid during the follicular phase (n = 14) ranged from 16.4 x 10(3) to 616.5 x 10(3) U/mL, and from 6.2 x 10(3) to 567.3 x 10(3) U/mL in the luteal phase (n = 11). In the paired sequential uterine fluid and serum samples, (1) the means (+/- SEM) CA-125 in uterine fluid were 81.5 x 10(3) +/- 37.9 x 10(3) U/mL and 91.4 x 10(3) +/- 56.8 x 10(3) U/mL in the midfollicular and midluteal phases, respectively (P = 0.75); (2) the CA-125 levels in serum increased in the midluteal phase (P less than 0.05); and (3) compared with serum, uterine fluid levels were greater with a wider range. CONCLUSIONS: When compared with serum CA-125, uterine fluid contains high concentrations varying over a wide range without fluctuation between the follicular and luteal phases of the menstrual cycle.     

Gonadotropin and ovarian hormone dynamics in luteal phase defects.

Blood samples were obtained during early follicular, periovulatory, and luteal phases in four women with out-of-phase endometrial biopsy specimens and four normal controls. In the study cycle, follicular development was evaluated and a late luteal phase endometrial biopsy was performed in each subject. Area under the luteal phase progesterone curve positively correlated with degree of maturity of the endometrial biopsy. Peak serum estradiol, maximum follicular diameter, and both immunoactivity and bioactivity of the preovulatory luteinizing hormone and follicle-stimulating hormone surges were similar in the luteal phase defect cycles as compared with normal cycles. Likewise luteinizing hormone bioactivity in the luteal phase of the luteal phase defect cycles was similar to that of normals. These data show that the immunoactivity and bioactivity of periovulatory and luteal phase gonadotropins may be normal in luteal phase defect cycles.     

Endocrine profiles in tamoxifen-induced conception cycles

Twenty-five infertile women conceived while taking tamoxifen (TMX). Daily serum profiles of 5 of the 25 TMX-induced conception cycles were elucidated and compared with those found in 5 normal cycles. In spite of lower levels of follicle-stimulating hormone and luteinizing hormone during the follicular phases, estradiol concentrations were higher in the TMX-induced conception cycles. It is suggested that this may be due to a direct ovarian effect of TMX as one of its major mechanisms in the course of folliculogenesis. On the other hand, progesterone concentrations on days 6 and 7 during the luteal phases were also higher in the TMX-induced conception cycles. It is suggested that this may be due to a luteotropic influence at the blastocyst stage.     

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.