Printer Friendly

Current preventive strategies for preovulatory progesterone elevation during ovarian stimulation for in vitro fertilization.

SUMMARY--The purpose of this review is to present contemporary measures for preventing the increase in preovulatory progesterone (P) and its adverse effects on ovarian stimulation in in vitro fertilization (IVF). For the last 20 years, the increase of preovulatory P has been a topic of numerous discussions because its role is not fully understood in terms of its impact on pregnancy outcome after IVF. Some studies failed to establish a connection between the preovulatory P increase and successful IVF outcome regardless of the level of P, while, conversely, most other studies have reported on adverse effects of elevated P concentrations. Current strategies to prevent the increase in preovulatory P include an individualized approach with the use of mild stimulation protocols and early application of human chorionic gonadotropin for ovulation induction among good responders, delay in the transfer of fresh embryos from 3 (rd) to 5 (th) day, and cryopreservation of all embryos with the thawed embryo transfer in the natural cycle. Nevertheless, further studies are needed to confirm the current preventive methods or enable the application of new strategies in order to lower or eliminate the detrimental effects of preovulatory P rise during ovarian stimulation in IVF.

Key words: Female; Fertilization, in vitro; Progesterone--biosynthesis; Ovulation induction; Embryo transfer; Cryopreservation

Introduction

Elevated preovulatory serum progesterone (P) is frequently ascertained during the late follicular phase at the end of ovarian stimulation on the day of ovulation triggering with human chorionic gonadotropin (hCG) during the in vitro fertilization (IVF) cycle. The incidence of premature P rise varies widely from 13% to 71% depending on definition, cut-off level of P, stimulation protocols and population characteristics (1). The presence of premature luteinizing hormone (LH) surge during ovarian stimulation has been previously correlated with preovulatory P rise and it has been constantly associated with reduced pregnancy rates (2). In order to prevent premature LH rise and consequently premature P rise, gonadotropin-releasing hormone (GnRH) analogues have been introduced. Although the significance of GnRH analogues in the prevention of preovulatory P rise has been proven, higher P levels have been recorded in approximately 35% of GnRH agonist cycles and 38% of GnRH antagonist cycles (3).

The ovarian response to follicle stimulating hormone (FSH) in recombinant (rec)-FSH/GnRH antagonist cycles has been associated with the risk of P elevation. Furthermore, a direct correlation between premature P rise and estradiol (E2) levels and the number of follicles on the day of hCG administration has been widely confirmed. The association between the high E2 and premature P elevation could be explained by an excess of proliferating granulosa cells that can lead to an increased P production (4). According to the two-cell, two-gonadotropin theory and the fact that excessive FSH stimulation may increase the production of P, the inclusion of LH activity products in stimulation protocols to counterbalance the effect of FSH may help reduce the risk of late follicular P increases (5). However, a systematic review of several studies comparing FSH administration alone or in combination with LH activity products could not demonstrate any significant effect of 'LH activity' on serum preovulatory P elevation. Therefore, the major determining factor for the risk of P rise at the time of hCG administration remains the degree of ovarian response to FSH (6). However, early addition of increasing doses of hCG (0,50,100 and 150 IU) from the beginning of ovarian stimulation in combination with rec FSH + GnRH antagonist was associated with an increased risk of P elevation (7). Furthermore, it appears that the choice of GnRH analogue has an impact on the risk of P elevation because preovulatory P levels were higher in women treated with GnRH agonist as compared with GnRH antagonist. These differences can be explained by stronger ovarian response to FSH as the main driver of P output and by higher endogenous LH concentration during the last few days of stimulation in favor of GnRH agonist (8,9). It appears that endogenous LH in the late follicular phase acts positively on P secretion and women treated with GnRH agonist protocols are more prone to P elevation (10).

Since the early 1990s, there has been an ongoing debate in more than 60 studies in women undergoing ovarian stimulation with controversial conclusions regarding the impact of preovulatory P on IVF outcome. Several previous and recent studies failed to demonstrate any negative effect of P rise (10-12). The first metaanalysis of 12 studies, published in 2007, has reported that there was a nonsignificant negative association between P elevation and pregnancy rate in women with GnRH analogues and gonadotropins (12). However, the second meta-analysis from 2012 focused on women using GnRH antagonists and gonadotropins (five studies) states that P elevation on the day of hCG administration is associated with a significantly decreased probability of clinical pregnancy per cycle (13). Similarly, in the third meta-analysis from 2013 of over 60 000 fresh IVF cycles it was found that P elevation on the day of hCG was associated with a significantly decreased probability of pregnancy in women, whatever the GnRH analogue used. The thresholds of serum P on the day of hCG administration were arbitrarily chosen from 0.4 ng/mL to 3 ng/mL and the strongest effect size of P elevation for achievement of pregnancy was observed with P thresholds between 1.5 ng/mL and 1.75 ng/mL (14). Several recent studies also established that P elevation on the day of hCG administration could be associated with a risk of reduced implantation rate. Despite the use of different thresholds of serum P, the optimal P threshold over which a detrimental effect on IVF outcome might be observed has been estimated to 1.5 ng/mL and this threshold has been commonly used (10,15,16). It seems that the P threshold in women using GnRH agonists is dependent on the degree of the ovarian response because in poor responders, the P threshold associated with a lower pregnancy rate was estimated at 1.5 ng/mL, in patients with normal ovarian response 1.75 ng/mL and in high responders 2.25 ng/mL (17). Consequently, in patients treated with rec FSH and GnRH antagonists, P elevation does not compromise pregnancy rates in high responders, although its incidence increases with ovarian response and elevated P at a threshold of 1.5 ng/mL is independently associated with a decreased chance of pregnancy in low-to-normal responders. Therefore, it seems that the detrimental effect of P elevation on the implantation rate could be compensated for by an increased yield of high-quality oocytes (18). Interestingly, the duration of P elevation could have a stronger impact on cycle outcome than the absolute serum P concentration on the day of hCG. The clinical pregnancy rate is significantly inversely correlated with the duration of premature serum P elevation above the cut-off value of 1.0 ng/mL, whatever the protocol used and the intensity of the ovarian response (19). It seems that the use of a multivariable analysis is the proper way of assessing the adverse effect of preovulatory P elevation on live birth rates, when compared with the bivariate analysis that was used in most of the studies that failed to identify the detrimental effect in fresh IVF cycles (20).

Since preovulatory P rise during ovarian stimulation is not associated with any significant changes in either oocyte or embryo quality, it is now convincingly accepted that P prematurely opens the window of implantation and modifies endometrial receptivity, leading to defective implantation and mainly contributing to the decreased pregnancy rate (14). Indeed, any 3-day advancement in endometrial receptivity assessed by endometrial biopsy at the time of oocyte retrieval results in a significant decrease in implantation rate, presumably related to P elevation (21,22). However, direct evidence for an effect of P rise on the endometrium has been provided by the altered gene expression profile in a recent functional genomics analysis (23,24). Since the majority of published studies demonstrated a detrimental effect of preovulatory P elevation which contributes to a decreased pregnancy rate, the purpose of this review is to analyze current preventive strategies that may improve pregnancy outcome following IVF.

Prevention of Preovulatory Progesterone Elevation

Mild ovarian stimulation protocols are associated with lower E2 levels and therefore may be useful in the prevention of premature P rise due to strong correlation between ovarian response and preovulatory P rise (25), which may be achieved with limited gonadotropins or with alternatives such as anti-estrogens or aromatase inhibitors since they reduce the dose of gonadotropins required for stimulation and keep estrogen levels low (26). There are limited clinical data available concerning the use of aromatase inhibitors in IVF treatment. Up to date, only three randomized controlled trials involving a total of 80 women studied the use of aromatase inhibitors in IVF (27). However, new studies yielded promising results on the benefit of aromatase inhibitor use in terms of ovarian stimulation for IVF (28,29). Although mild stimulation is correlated with a reduced risk of premature P rise, lower pregnancy rates per cycle, fewer embryos for cryopreservation and still not available individualized FSH-dosing algorithms have been reported (27). Moreover, it is important to consider each patient's general condition including age, ovarian reserve, embryo grading and the capacity of frozen/thawed embryo transfer when mild protocols are used for stimulation (30).

An earlier hCG trigger, when follicles reach a diameter of 15-16 mm, has been suggested as a strategy for preventing premature P rise. It has been suggested that earlier hCG trigger should take place when [greater than or equal to]3 follicles of [greater than or equal to]16 mm diameter are present on ultrasonography (31). However, this early trigger has been associated only with lower preovulatory P but not with better ongoing pregnancy rates (32). In order to avoid premature P rise and its detrimental effect on IVF outcome, earlier trigger in high responders is more suitable as compared with normal and poor responders (31,33). Due to the potential predictive role of E2 concentrations for premature P rise, final oocyte maturation can be triggered when the E2 concentration reaches the point of having a risk of preovulatory P rise (34).

One of the strategies that have been suggested to overcome the detrimental effect of advanced endometrial maturation is to enable endometrial recovery before transfer. Numerous studies investigated the benefit of day 5 compared to day 3 embryo transfer (ET) (35-37) ; increased probability of pregnancy with day 5 ET was recorded in 2 independent trials (36,38). In other words, a higher rate of early pregnancy loss was recorded after day 3 single ET as compared with day 5 single blastocyst transfer in GnRH antagonist stimulated IVF cycles. Two different systematic reviews and meta-analysis independently confirmed previous findings; improved IVF outcome was associated with day 5 ET and not with day 3 ET (38,39). Analyzing both developmental stage and fragmentation rate, the implantation potential of advanced blastocysts was influenced by developmental stage on day 5 and fragmentation rate on day 3 ET (40). Lower implantation rate on day 3 ET is most likely associated with disturbed embryoendometrium synchrony in terms of high preovulatory P. Furthermore, as the endometrium seems to be recovered from the supraphysiological P values on day 5, a better implantation rate is quite expected with day 5 single blastocyst transfer (41). However, only a few studies failed to confirm the preference of day 5 ET as a potential strategy to overcome the deleterious effect of elevated P on IVF pregnancy outcome. Therefore, better embryo implantation and live birth rate could not be confirmed on day 5 fresh ET in terms of the rise of serum P levels >2.0 ng/mL on the day of hCG administration in cycles with GnRH agonists (42). Similarly, a study from 2013 failed to demonstrate the preference of day 5 ET as a strategy to overcome the detrimental effect of P rise on IVF pregnancy outcome (33). Nevertheless, as the majority of studies yielded better implantation rate and IVF pregnancy outcome with day 5 single blastocyst transfer as compared with day 3 single ET, the selection of blastocyst transfer as a strategy for overcoming the adverse effect of high preovulatory P seems to be quite justified (36,37,41).

Elective cryopreservation of all embryos with subsequent transfer in a natural cycle or during ovulation induction has been proposed as a solution to avoid the negative effect of high preovulatory P on IVF outcome, as well as in the prevention of ovarian hyperstimulation syndrome (42,43). Indeed, various studies yielded significantly higher ongoing and clinical pregnancy rates when frozen ET was used as compared with fresh ET (44-46). It seems that the adverse effect of P elevation on endometrium in terms of IVF outcome could be overcome by frozen-thawed embryo transfer (FET) in a later non-stimulated cycle, since the embryo-endometrium synchrony is thus re-established, although poor quality embryos could not be eliminated through the utilization of cryopreservation (46). In the past decade, the number of frozen-thawed embryo transfer cycles per started IVF cycle has increased steadily and at the same time the percentage of frozen-thawed embryo transfers that resulted in live births has increased. Currently, cryopreservation of human embryos is more important than ever for the cumulative pregnancy rate after IVF. It seems that freeze-all strategy, in which all embryos are frozen and no fresh transfer is conducted, has been proven to increase success rates in IVF cycles (47).

Conclusion

Current strategies in the prevention of preovulatory P rise include an individualized approach with the use of mild stimulation protocols with intensive monitoring of folliculogenesis and earlier use of hCG for ovulation induction in high responders. However, to avoid the negative endometrial effects of P rise, it should be useful to delay ET from day 3 to day 5. Finally, the most appropriate choice would be to cancel fresh ET and freeze all embryos with FET in the natural cycle. However, there is the need for further research which would confirm the current preventive methods or enable the application of new strategies in order to lower or eliminate the detrimental effects of preovulatory P rise during ovarian stimulation in IVF procedure.

References

(1.) Check JH, Chase JS, Nowroozi K, Dietterich CJ. Premature luteinization: treatment and incidence in natural cycles. Hum Reprod. 1991;6:190-3.

(2.) Sonmezer M, Cil AP, Atabekoglu C, Ozkavukcu S, Ozmen B. Does premature luteinization or early surge of LH impair cycle outcome? Report of two successful outcomes. J Assist Reprod Genet. 2009;26:159-63.

(3.) Saharkhiz N, Salehpour S, Tavasoli M, Aghighi A. Premature progesterone rise at human chorionic gonadotropin triggering day has no correlation with intracytoplasmic sperm injection outcome. Iran J Reprod Med. 2015;13:79-84.

(4.) Kyrou D, Popovic-Todorovic B, Fatemi HM, et al. Does the estradiol level on the day of human chorionic gonadotropin administration have an impact on pregnancy rates in patients treated with rec-FSH/GnRH antagonist? Hum Reprod. 2009;24:2902-9. doi: 10.1093/humrep/dep290

(5.) Werner MD, Forman EJ, Hong KH, Franasiak JM, Molinaro TA, Scott RT Jr. Defining the "sweet spot" for administered luteinizing hormone-to-follicle-stimulating hormone gonadotropin ratios during ovarian stimulation to protect against a clinically significant late follicular increase in progesterone: an analysis of 10,280 first in vitro fertilization cycles. Fertil Steril. 2014;102:1312-7. doi: 10.1016/j.fertnstert.2014.07.766

(6.) Hugues JN. Impact of 'LH activity' supplementation on serum progesterone levels during controlled ovarian stimulation: a systematic review. Hum Reprod. 2012;27:232-43. doi: 10.1093/humrep/der3 80

(7.) Thuesen LL, Smitz J, Loft A, Nyboe Andersen A. Endocrine effects of hCG supplementation to recombinant FSH throughout controlled ovarian stimulation for IVF: a dose-response study. Clin Endocrinol (Oxf). 2013;79:708-15. doi: 10.1111/cen. 12186

(8.) Hugues JN, Masse-Laroche E, Reboul-Marty J, Boiko O, Meynant C, Cedrin-Durnerin I. Impact of endogenous luteinizing hormone serum levels on progesterone elevation on the day of human chorionic gonadotropin administration. Fertil Steril. 2011;96:600-4. doi: 10.1016/j.fertnstert.2011.06.061

(9.) Papanikolaou EG, Pados G, Grimbizis G, et al. GnRH-agonist versus GnRH-antagonist IVF cycles: is the reproductive outcome affected by the incidence of progesterone elevation on the day of hCG triggering? A randomized prospective study. Hum Reprod. 2012;27:1822-8. doi: 10.1093/humrep/des066

(10.) Yding Andersen C, Bungum L, Nyboe Andersen A, Humaidan P. Preovulatory progesterone concentration associates significantly to follicle number and LH concentration but not to pregnancy rate. Reprod Biomed Online. 2011;23:187-95. doi: 10.1016/j.rbmo.2011.04.003

(11.) Martinez F, Coroleu B, Clua E, et al. Serum progesterone concentrations on the day of hCG administration cannot predict pregnancy in assisted reproduction cycles. Reprod Biomed Online. 2004;8:183-90.

(12.) Veneris CA, Kolibianakis EM, Papanikolaou E, Bontis J, Devroey P, Tarlatzis BC. Is progesterone elevation on the day of human chorionic gonadotropin administration associated with the probability of pregnancy in in vitro fertilization? A systematic review and meta-analysis. Hum Reprod Update. 2007; 13:343-55.

(13.) Kolibianakis EM, Veneris CA, Bontis J, Tarlatzis BC. Significantly lower pregnancy rates in the presence of progesterone elevation in patients treated with GnRH antagonists and gonadotropins: a systematic review and meta-analysis. Curr Pharm Biotechnol. 2012;13:464-70.

(14.) Veneris CA, Kolibianakis EM, Bosdou JK, Tarlatzis BC. Progesterone elevation and probability of pregnancy after IVF: a systematic review and meta-analysis of over 60 000 cycles. Hum Reprod Update. 2013;19:433-57. doi: 10.1093/humupd/dmt014

(15.) Bosch E, Labarta E, Crespo J, et al. Circulating progesterone levels and ongoing pregnancy rates in controlled ovarian stimulation cycles for in vitro fertilization: analysis of over 4000 cycles. Hum Reprod. 2010;25:2092-100. doi: 10.1093/humrep/deql25

(16.) Keltz MD, Stein DE, Berin I, Skorupski J. Elevated progesterone-to-estradiol ratio versus serum progesterone alone for predicting poor cycle outcome with in vitro fertilization. J Reprod Med. 2012;57:9-12.

(17.) Xu B, Li Z, Zhang H, et al. Serum progesterone level effects on the outcome of in vitro fertilization in patients with different ovarian response: an analysis of more than 10,000 cycles. Fertil Steril. 2012;97:1321-7. doi: 10.1016/j.fertnstert.2012.03.014

(18.) Griesinger G, Mannaerts B, Andersen CY, Witjes H, Kolibianakis EM, Gordon K Progesterone elevation does not compromise pregnancy rates in high responders: a pooled analysis of in vitro fertilization patients treated with recombinant follicle-stimulating hormone/gonadotropin-releasing hormone antagonist in six trials. Fertil Steril. 2013;100:1622-8. doi: 10.1016/j.fertnstert.2013.08.045

(19.) Huang CC, Lien YR, Chen HF, et al. The duration of preovulatory serum progesterone elevation before hCG administration affects the outcome of IVF/ICSI cycles. Hum Reprod. 2012;27:2036-45. doi: 10.1093/humrep/desl41

(20.) Veneris CA, Kolibianakis EM, Bosdou JK, et al. Estimating the net effect of progesterone elevation on the day of hCG on live birth rates after IVF: a cohort analysis of 3296 IVF cycles. Hum Reprod. 2015;30:684-91. doi: 10.1093/humrep/deu362

(21.) Kolibianakis E, Bourgain C, Albano C, et al. Effect of ovarian stimulation with recombinant follicle-stimulating hormone, gonadotropin releasing hormone antagonists, and human chorionic gonadotropin on endometrial maturation on the day of oocyte pick-up. Fertil Steril. 2002;78:1025-9.

(22.) Sonigo S, Dray G, Roche C, Cedrin-Durnerin I, Hugues JN. Impact of high serum progesterone during the late follicular phase on IVF outcome. Reprod Biomed Online. 2014;29:177-86. http://dx.doi.Org/10.1016/j.rbmo.2014.03.027

(23.) Labarta E, Martinez-Conejero JA, Alama P, et al. Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod 2011;26:1813-25. doi: 10.1093/humrep/derl26

(24.) Van Vaerenbergh I, Fatemi HM, Blockeel C, et al. Progesterone rise on hCG day in GnRH antagonist/rFSH stimulated cycles affects endometrial gene expression. Reprod Biomed Online. 2011;22:263-71. doi: 10.1016/j.rbmo.2010.11.002

(25.) Kolibianakis EM, Albano C, Camus M, Tournaye H, Van Steirteghem AC, Devroey P. Prolongation of the follicular phase in in vitro fertilization results in a lower ongoing pregnancy rate in cycles stimulated with recombinant follicle-stimulating hormone and gonadotropin-releasing hormone antagonists. Fertil Steril. 2004;82:102-7.

(26.) Mahajan N. Should mild stimulation be the order of the day? J Hum Reprod Sci. 2013;6:220-6. doi: 10.4103/0974-1208.12628

(27.) Verberg MF, Macklon NS, Nargund G, et al. Mild ovarian stimulation for IVF. Hum Reprod Update. 2009;15:13-29. doi: 10.1093/humupd/dmn056

(28.) Papanikolaou EG, Polyzos NP, Humaidan P, et al. Aromatase inhibitors in stimulated IVF cycles. Reprod Biol Endocrinol. 2011;9:85. doi: 10.1186/1477-7827-9-85

(29.) Hamdine O, Broekmans FJ, Fauser BC. Ovarian stimulation for IVF: mild approaches. Methods Mol Biol. 2014;1154: 305-28. doi: 10.1007/978-1-4939-0659-8_14

(30.) Fauser BCJM, Nargund G, Andersen AN, et al. Mild ovarian stimulation for IVF: 10 years later. Hum Reprod. 2010;25: 2678-84. doi: 10.1093/humrep/deq247

(31.) Kyrou D, Kolibianakis EM, Fatemi HM, Tarlatzis BC, Tournaye H, Devroey P. Is earlier administration of human chorionic gonadotropin (hCG) associated with the probability of pregnancy in cycles stimulated with recombinant follicle-stimulating hormone and gonadotropin-releasing hormone (GnRH) antagonists? A prospective randomized trial. Fertil Steril. 2011;96:1112-5. doi: 10.1016/j.fertnstert.2011.08.029

(32.) Lin YJ, Lan KC, Huang FJ, Lin PY, Chiang HJ, Kung FT Reproducibility and clinical significance of pre-ovulatory serum progesterone level and progesterone/estradiol ratio on the day of human chorionic gonadotropin administration in infertile women undergoing repeated in vitro fertilization cycles. Reprod Biol Endocrinol. 2015;13:41. doi: 10.1186/s12958-015-0037-9

(33.) Al-Azemi M, Kyrou D, Kolibianakis EM, et al. Elevated progesterone during ovarian stimulation for IVF. Reprod Biomed Online. 2012;24:381-8. doi: 10.1016/j.rbmo.2012.01.010

(34.) Al-Azemi M, Kyrou D, Papanikolaou EG. The relationship between premature progesterone rise with serum estradiol levels and number of follicles in GnRH antagonist/rec-FSH stimulated cycles. 27 (th) Annual Meeting of ESHRE 2011. Hum Reprod. 2011;26:I324. doi: 10.1016/j.ejogrb.2012.02.025

(35.) Corti L, Papaleo E, Pagliardini, et al. Fresh blastocyst transfer as a clinical approach to overcome the detrimental effect of progesterone elevation at hCG triggering: a strategy in the context of the Italian law. Eur J Obstet Gynecol Reprod Biol. 2013;171:73-7. doi: 10.1016/j.ejogrb.2013.08.017

(36.) Papanikolaou EG, Kolibianakis EM, Pozzobon C, et al. Progesterone rise on the day of human chorionic gonadotropin administration impairs pregnancy outcome in day 3 singleembryo transfer, while has no effect on day 5 single blastocyst transfer. Fertil Steril. 2009;91:949-52.

(37.) Elgindy EA, Abou-Setta AM, Mostafa MI. Blastocyst-stage versus cleavage-stage embryo transfer in women with high oestradiol concentrations: randomized controlled trial. Reprod Biomed Online. 2011;23:789-98. doi: 10.1016/j.rbmo.2011. 08.011

(38.) Glujovsky D, Blake D, Bardach A, Farquhar C. Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology. Cochrane Database of Systematic Reviews 2012. Art. No.: CD002118. doi: 10.1002/14651858.CD002118.pub4

(39.) Wang SS, Sun HX. Blastocyst transfer ameliorates live birth rate compared with cleavage-stage embryos transfer in fresh in vitro fertilization or intracytoplasmic sperm injection cycles: reviews and meta-analysis. Yonsei Med J. 2014;55:815-25. doi: 10.3349/ymj.2014.55.3.815

(40.) della Ragione T, Verheyen G, Papanikolaou EG, Van Landuyt L, Devroey P, Van Steirteghem A. Developmental stage on day-5 and fragmentation rate on day-3 can influence the implantation potential of top-quality blastocysts in IVF cycles with single embryo transfer. Reprod Biol Endocrinol. 2007;5:2. doi: 10.1186/1477-7827-5-2

(41.) Kaur P, Swarankar ML, Maheshwari M, Acharya V A comparative study between cleavage stage embryo transfer at day 3 and blastocyst stage transfer at day 5 in in vitro fertilization/intracytoplasmic sperm injection on clinical pregnancy rates. J Hum Reprod Sci. 2014;7:194-7. doi: 10.4103/0974-1208.142481

(42.) Roque M, Valle M, Guimaraes F, Sampaio M, Geber S. Freezeall policy: fresh vs frozen-thawed embryo transfer. Fertil Steril. 2015;103:1190-3. doi: 10.1016/j.fertnstert.2015.01.045

(43.) Kasum M, Oreskovic S. Treatment of ovarian hyperstimulation syndrome: new insights. Acta Clin Croat. 2010;49:421-7.

(44.) Requena A, Cruz M, Bosch E, Meseguer M, Garcia-Velasco JA. High progesterone levels in women with high ovarian response do not affect clinical outcomes: a retrospective cohort study. Reprod Biol Endocrinol. 2014;12:69. doi: 10.1186/14777827-12-69

(45.) Lahoud R, Kwik M, Ryan J, Al-Jefout M, Foley J, Illingworth P. Elevated progesterone in GnRH agonist down regulated in vitro fertilisation (IVFICSI) cycles reduces live birth rates but not embryo quality. Arch Gynecol Obstet. 2012;285:535-40. doi: 10.1007/s00404-011-2045-0

(46.) Roque M, Lattes K, Serra S, et al. Fresh embryo transfer versus frozen embryo transfer in in vitro fertilization cycles: a systematic review and meta-analysis. Fertil Steril. 2013;99:156-62. doi:10.1016/j.fertnstert.2012.09.003

(47.) Wong KM, Mastenbroek S, Repping S. Cryopreservation of human embryos and its contribution to in vitro fertilization success rates. Fertil Steril. 2014;102:19-26. doi: 10.1016/j. fertnstert.2014.05.027

Sazetak

SUVREMENE PREVENCIJSKE STRATEGIJE PORASTA PREDOVULACIJSKOG PROGESTERONA TIJEKOM STIMULACIJE JAJNIKA U POSTUPKU IZVANTJELESNE OPLODNJE

E. Ejubovic, M. Kasum, P. Stanic, J. Juras, E. Cehic i S. Oreskovic

Svrha ovoga preglednog clanka je prikazati suvremene mjere za prevenciju porasta predovulacijskog progesterona (P) i njegovih nepovoljnih ucinaka kod stimulacije jajnika u postupku izvantjelesne oplodnje. Unatrag 20-ak godina porast predovulacijskog P tema je brojnih rasprava, jer njegova uloga nije u potpunosti razjasnjena u pogledu utjecaja na ishod trudnoce nakon postupka izvantjelesne oplodnje. Neka istrazivanja nisu utvrdila nikakvu povezanost izmedu porasta predovulacijskog P u odnosu na uspjesnost postupka izvantjelesne oplodnje neovisno o razini P, dok nasuprot tome, vecina drugih istrazivanja izvjescuje o nepovoljnim ucincima povisene koncentracije P. Suvremene strategije u prevenciji porasta predovulacijskog P ukljucuju individualizirani pristup primjenom blazih stimulacijskih protokola te raniju primjenu humanog korionskog gonadotropina za indukciju ovulacije kod bolesnica koje dobro reagiraju na stimulaciju, odgodu prijenosa svjezih zametaka s 3. na 5. dan i krioprezervaciju svih zametaka uz transfer odmrznutih embrija u prirodnom ciklusu. Neophodna su daljnja istrazivanja koja ce potvrditi postojece prevencijske metode ili omoguciti primjenu novih strategija, sa svrhom onemogucavanja nepovoljnog utjecaja porasta predovulacijskog P na ishod trudnoce nakon postupka izvantjelesne oplodnje.

Kljucne rijeci: Zenska osoba; Fertilizacija, in vitro; Progesteron--biosinteza; Ovulacija, indukcija; Zametak, transfer; Krioprezervacija

Emina Ejubovic (1), Miro Kasum (2), Patrik Stanic (2), Josip Juras (2), Ermin Cehic (3) and Slavko Oreskovic (2)

(1) Department for Female Diseases, Perinatology and Neonatology, Zenica Cantonal Hospital, Zenica, Bosnia and Herzegovina; (2) Clinical Department of Obstetrics and Gynecology, Zagreb University Hospital Center, School of Medicine, University of Zagreb, Zagreb, Croatia; (3) Center for Female Reproduction, Zenica Cantonal Hospital, Zenica, Bosnia and Herzegovina

Correspondence to: Emina Ejubovic, MD, Department for Female Diseases, Perinatology and Neonatology, Zenica Cantonal Hospital, Crkvice 67,72 000 Zenica, Bosnia and Herzegovina

E-mail: ejubovic.emina@gmail.com

Received December 12,2015, accepted February 8,2016
COPYRIGHT 2016 Klinicki bolnicki centar Sestre milosrdnice
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2016 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:Ejubovic, Emina; Kasum, Miro; Stanic, Patrik; Juras, Josip; Cehic, Ermin; Oreskovic, Slavko
Publication:Acta Clinica Croatica
Date:Nov 1, 2016
Words:4494
Previous Article:Measuring physical activity in pregnancy using questionnaires: A meta-analysis.
Next Article:Oral lesions in kidney transplant recipients.
Topics:

Terms of use | Privacy policy | Copyright © 2019 Farlex, Inc. | Feedback | For webmasters