Increased progesterone/estradiol ratio in the late follicular phase could be related to low ovarian reserve in in vitro fertilization–embryo transfer cycles with a long gonadotropin-releasing hormone agonist

Younis, Johnny S.; Matilsky, Moshe; Radin, Orit; Ben‐Ami, Moshe

doi:10.1016/s0015-0282(01)01918-5

Cited by 104 publications

(91 citation statements)

References 27 publications

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“…Women with premature luteinization, indeed, may have higher day 3 FSH levels (Younis et al 1998(Younis et al , 2001, though there are no data to support higher intracycle levels in the literature. In this study, FSH levels during ovarian hyperstimulation were not higher in Group 3 patients.…”

Section: Discussionmentioning

confidence: 97%

Aging-related premature luteinization of granulosa cells is avoided by early oocyte retrieval

Wu¹,

Barad²,

Kushnir³

et al. 2015

Journal of Endocrinology

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Why IVF pregnancy rates decline sharply after age 43 is unknown. In this study, we compared granulosa cell (GC) function in young oocyte donors (nZ31, ages 21-29), middle-aged (nZ64, ages 30-37) and older infertile patients (nZ41, ages 43-47). Gene expressions related to gonadotropin activity, steroidogenesis, apoptosis and luteinization were examined by real-time PCR and western blot in GCs collected from follicular fluid. FSH receptor (FSHR), aromatase (CYP19A1) and 17b-hydroxysteroid dehydrogenase (HSD17B) expression were found down regulated with advancing age, while LH receptor (LHCGR), P450scc (CYP11A1) and progesterone receptor (PGR) were up regulated. Upon in vitro culture, GCs were found to exhibit lower proliferation and increased apoptosis with aging. While FSH supplementation stimulated GCs growth and prevented luteinization in vitro. These observations demonstrate age-related functional declines in GCs, consistent with premature luteinization. To avoid premature luteinization in women above age 43, we advanced oocyte retrieval by administering human chorionic gonadotropin at maximal leading follicle size of 16 mm (routine 19-21 mm). Compared to normal cycles in women of similar age, earlier retrieved patients demonstrated only a marginal increase in oocyte prematurity, yet exhibited improved embryo numbers as well as quality and respectable clinical pregnancy rates. Premature follicular luteinization appears to contribute to rapidly declining IVF pregnancy chances after age 43, and can be avoided by earlier oocyte retrieval.

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Section: Discussionmentioning

confidence: 97%

Aging-related premature luteinization of granulosa cells is avoided by early oocyte retrieval

Wu¹,

Barad²,

Kushnir³

et al. 2015

Journal of Endocrinology

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“…The ovarian response, number of retrieved oocytes, number of mature oocytes retrieved, and number of fertilized eggs were significantly lower in the patients with a P/F ratio>.075. Some studies using the P/E 2 ratio have found similar results after establishing a cut-off value for P/E 2 , suggesting that this ratio is associated with lower fertility [19,26]. Studies attempting to establish cut-off levels or ratios using hormonal measurements may be influenced by the different measurement techniques used or by the lab at which they are measured.…”

Section: Discussionmentioning

confidence: 99%

Ratio of progesterone-to-number of follicles as a prognostic tool for in vitro fertilization cycles

Roque

Valle

Sampaio

et al. 2015

J Assist Reprod Genet

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Purpose To establish a ratio of the P level to the number of follicles (P/F ratio) on the day of human chorionic gonadotropin (hCG) administration and to evaluate whether this ratio is associated with in vitro fertilization (IVF) outcome. Methods This study was conducted between January 2012 and June 2013. A total of 337 patients with cleavage-stage day-3 fresh embryo transfer with P levels ≤1.5 ng/mL on the day of hCG administration were included in the study. The main outcome was ongoing pregnancy rate. Result(s) The P/F ratio was calculated according to the equation (P[ng/mL]/number of follicles) on the day of final oocyte maturation. Using ROC, we established a cut-off level of 0.075 for the P/F ratio. The area under the curve (AUC) (0.756; 95 % confidence interval [CI]: 0.704-0.807) indicated that it was a good prognostic test. In group 1 (patients under 36 years old), the ongoing pregnancy rates were 57 and 30 % for patients with P/F ratios≤.075 and>.075, respectively, (p= 0.003). In group 2 (patients between 36 and 39 years old), the ongoing pregnancy rates were 58 % and 17 % (p=0.001) for patients with P/F ratios ≤.075 and>.075, respectively. In group 3 (patients≥40 years old), the ongoing pregnancy rates were 41.7 and 10.9 % (p=0.001) for patients with P/F ratios≤.075 and>.075, respectively. Conclusions The P/F ratio is a good prognostic test for predicting IVF outcome that can correlate the P level with ovarian response.

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“…Prospective controlled studies employing the long GnRH agonist [10] as well as the antagonist [11] protocols did not show LH elevation despite P rise on the day of hCG administration in the presumed "premature luteinization" cycles. Moreover, LH addition to FSH treatment following GnRH agonist down-regulation did not increase P level during the follicular phase or on the day of hCG administration, as compared to FSH only stimulation [12][13][14].…”

Section: Introductionmentioning

confidence: 86%

“…During the GnRH analogue era the term of premature luteinization was nonintentionally dragged from the previous period with the same definition. Although most investigators still apply an absolute P level on hCG day as an indication for elevated P level, the cut-off point has differed considerably between one study and another ranging from 0.9 to 2.0 ng/mL [1,10]. Most recent studies have suggested that a cut-off point of 1.25 [16] or 1.5 ng/mL [2], may differentiate more properly in their detrimental effect on endometrial receptivity, however this should be investigated further taking into account the type of gonadotropin and GnRH analogue (agonist or antagonist) employed.…”

Section: A Call For a New Definitionmentioning

confidence: 99%

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“Premature luteinization” in the era of GnRH analogue protocols: time to reconsider

Younis

2011

J Assist Reprod Genet

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Increased progesterone/estradiol ratio in the late follicular phase could be related to low ovarian reserve in in vitro fertilization–embryo transfer cycles with a long gonadotropin-releasing hormone agonist

Cited by 104 publications

References 27 publications

Aging-related premature luteinization of granulosa cells is avoided by early oocyte retrieval

Aging-related premature luteinization of granulosa cells is avoided by early oocyte retrieval

Ratio of progesterone-to-number of follicles as a prognostic tool for in vitro fertilization cycles

“Premature luteinization” in the era of GnRH analogue protocols: time to reconsider

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