![[PDF]](/pb-assets/Icons/adobe-pdf-icon-1498649896243.png){kind=icon}
Abstract
The purpose of this review was to determine whether there is evidence that ovulation can occur in women using hormonal contraceptives and whether these drugs might inhibit implantation. We performed a systematic review of the published English-language literature from 1990 to the present which included studies on the hormonal milieu following egg release in women using any hormonal contraceptive method. High circulating estrogens and progestins in the follicular phase appear to induce dysfunctional ovulation, where follicular rupture occurs but is followed by low or absent corpus luteum production of progesterone. Hoogland scoring of ovulatory activity may inadvertently obscure the reality of ovum release by limiting the term “ovulation” to those instances where follicular rupture is followed by production of a threshold level of luteal progesterone, sufficient to sustain fertilization, implantation, and the end point of a positive β-human chorionic gonadotropin. However, follicular ruptures and egg release with subsequent low progesterone output have been documented in women using hormonal contraception. In the absence of specific ovulation and fertilization markers, follicular rupture should be considered the best marker for egg release and potential fertilization. Women using hormonal contraceptives may produce more eggs than previously described by established criteria; moreover, suboptimal luteal progesterone production may be more likely than previously acknowledged, which may contribute to embryo loss. This information should be included in informed consent for women who are considering the use of hormonal contraception.
Summary:
For this study, the authors looked at English-language research articles that focused on how hormonal birth control, such as the birth control pill, may affect very early human embryos. The authors found that abnormal ovulation, or release of an egg followed by abnormal hormone levels, may often occur in women using hormonal birth control. This may increase the number of very early human embryos who are lost before a pregnancy test becomes positive. For women who are thinking about using hormonal birth control, this is important information to consider.
References
|
Achache, H., Revel, A.. 2006. “Endometrial Receptivity Markers, the Journey to Successful Embryo Implantation.” Human Reproduction Update 12, no. 6: 731–46. Google Scholar | Crossref | Medline | |
|
American Society for Reproductive Medicine in collaboration with the Society for Reproductive Endocrinology and Infertility . 2008. “Progesterone Supplementation during the Luteal Phase and in Early Pregnancy in the Treatment of Infertility: An Educational Bulletin.” Fertility and Sterility 90 (Suppl. 5): S150–53. Google Scholar | |
|
Andersen, C., Andersen, Vilbour K.. 2014. “Improving the Luteal Phase after Ovarian Stimulation: Reviewing New Options.” Reproductive Biomedicine Online 28, no. 5: 552–59. Google Scholar | Crossref | |
|
Anzai, Y., Heger-Mahn, D., Schellschmidt, I., Marr, J.. 2012. “Suppression of Ovarian Activity with a Low Dose 21/7-day Regiment Oral Contraceptive Containing Ethinylestradiol 20mcg/Drospirenon 3 mg in Japanese and Caucasian Women.” Contraception 86:28–34. Google Scholar | Crossref | |
|
Arce, J. C., Balen, A., Platteau, P., Pettersson, G., Andersen, A. N.. 2011. “Mid-luteal Progesterone Concentrations Are Associated with Live Birth Rates during Ovulation Induction.” Reproductive Biomedicine Online 22, no. 5: 449–56. Google Scholar | Crossref | |
|
Archer, D. F., Kovalevsky, G., Ballagh, S. A., Grubb, G. S.. 2009. “Ovarian Activity and Safety of a Novel Levonorgestrel/Ethinyl Estradiol Continuous Oral Contraceptive Regimen.” Contraception 80, no. 3: 245–53. Google Scholar | Crossref | |
|
Benagiano, G., Pera, A., Primiero, M.. 2000. “The Endometrium and Hormonal Contraceptives.” Human Reproduction 15 (Suppl. 1): 101–18. Google Scholar | Crossref | |
|
Birtch, R. L., Olatunbosun, O. A., Pierson, R. A.. 2006. “Ovarian Follicular Dynamics during Conventional vs. Continuous Oral Contraceptive Use.” Contraception 73, no. 3: 235–43. Google Scholar | Crossref | Medline | |
|
Bitzer, J., Simon, J. A.. 2011. “Current Issues and Available Options in Combined Hormonal Contraception.” Contraception 84, no. 4: 342–56. Google Scholar | Crossref | Medline | |
|
Blackwell, L. F., Cooke, D. G., Brown, S.. 2018. “The Use of Estrone-3-glucuronide and Pregnanediol-3-glucuronide Excretion Rates to Navigate the Continuum of Ovarian Activity.” Frontiers in Public Health 6:153. Google Scholar | Crossref | |
|
Check, J. H., Adelson, H. G., Dietterich, C., Stern, J.. 1990. “Pelvic Sonography Can Predict Ovum Release in Gonadotrophin-treated Patients as Determined by Pregnancy Rate.” Human Reproduction 5, no. 3: 234–36. Google Scholar | Crossref | |
|
Croxatto, H. B., Brache, V., Massai, R., Alvarez, F., Forcelledo, M. L., Pavez, M., Cochon, L., Salvatierra, A. M.. 2006. “Feasibility Study of Nestorone-ethinylestradiol Vaginal Contraceptive Ring for Emergency Contraception.” Contraception 73, no. 1: 46–52. Google Scholar | Crossref | |
|
Croxatto, H. B., Brache, V., Pavez, M., Cochon, L., Forcelledo, M. L., Alverez, F., Massai, R., Faundes, A., Salvatierra, A. M.. 2004. “Pituitary-ovarian Function Following a Standard Levonorgestre in Emergency Contraception Dose or a Single 0.75 mg Dose Given on the Days Preceding Ovulation.” Contraception 70, no. 6: 442–50. Google Scholar | Crossref | Medline | |
|
Croxatto, H. B., Salvatierra, A. M., Fuentealba, B., Massai, R.. 1998. “Contraceptive Potential of a Mifepristone-nomegestrol Acetate Sequential Regimen in Women.” Human Reproduction 13, no. 12: 3297–302. Google Scholar | Crossref | |
|
D’Hooghe, T. M., Charanjit, C. S., Raymaekers, B. M., Koninckx, P. R.. 1996. “Increased Incidence and Recurrence of Recent Corpus Luteum without Ovulation Stigma (Luteinized Unruptured Follicle Syndrome?) in Baboons with Endometriosis.” Journal of the Society for Gynecologic Investigation 3, no. 3: 140–44. Google Scholar | Crossref | Medline | |
|
Devoto, L., Kohen, P., Munoz, A., Strauss, J. F.. 2009. “Human Corpus Luteum Physiology and the Luteal-phase Dysfunction Associated with Ovarian Stimulation.” Reproductive Biomedicine Online 18 (Suppl. 2): 19–24. Google Scholar | Crossref | |
|
Duijkers, I. J., Heger-Mahn, D., Drouin, D., Skouby, S.. 2015. “A Randomised Study Comparing the Effect on Ovarian Activity of a Progestogen-only Pill (POP) Containing Desogestrel and a New POP Containing Drospirenone in a 24/4 Regimen.” The European Journal of Contraception & Reproductive Health Care 20, no. 6: 419–27. doi: 10.3109/13625187.2015.1044082. Google Scholar | Crossref | |
|
Duijkers, I. J., Klipping, C., Zimmerman, Y., Appels, N., Jost, M., Maillard, C., Mawet, M., Foidart, J. M., Coelingh Bennink, H. J.. 2015. “Inhibition of Ovulation by Administration of Estetrol in Combination with Drospirenone or Levonorgestrel: Results of a Phase II Dose-Finding Pilot Study.” The European Journal of Contraception & Reproductive Health Care 20, no. 6: 476–89. doi: 10.3109/13625187.2015.1074675. Google Scholar | Crossref | |
|
Endrikat, J., Gerlinger, C., Plettig, K., Wessel, J., Schmidt, W., Grubb, G., Düsterberg, B.. 2003. “A Meta-analysis on the Correlation between Ovarian Activity and the Incidence of Intermenstrual Bleeding during Low-dose Oral Contraceptive Use.” Gynecological Endocrinology 17, no. 2: 107–14. doi: 10.1080/gye.17.2.107.114. Google Scholar | Crossref | Medline | |
|
Endrikat, J., Parke, S., Trummer, D., Serrani, M., Duijkers, I., Klipping, C.. 2013. “Pituitary, Ovarian and Additional Contraceptive Effects of an Estradiol-based Combined Oral Contraceptive: Results of a Randomized, Open-label Study.” Contraception 87, no. 2: 227–34. Google Scholar | Crossref | Medline | |
|
ESHRE Capri Workshop Group . 2001. “Ovarian and Endometrial Function during Hormonal Contraception.” Human Reproduction 16, no. 7: 1527–35. Google Scholar | Crossref | |
|
Fatemi, H. M., Polyzos, N. P., van Vaerenbergh, I., Bourgain, C., Blockeel, C., Alsbjerg, B., Papanikolaou, E. G., Humaidan, P.. 2013. “Early Luteal Phase Endocrine Profile Is Affected by the Mode of Triggering Final Oocyte Maturation and the Luteal Phase Support Used in Recombinant Follicle-stimulating Hormone–Gonadotrophin-releasing Hormone Antagonist In Vitro Fertilization Cycles.” Fertility and Sterility 100, no. 3: 742–47. doi: 10.1016/j.fertnstert.2013.05.028. Google Scholar | Crossref | |
|
Goldstein, J., Pandy, P., Fleming, N., Westin, S., Piha-Paul, S.. 2016. “A Non-pregnant Woman with Elevated Beta-HCG: A Case of Para-neoplastic Syndrome in Ovarian Cancer.” Gynecologic Oncology Reports 17:49–52. Google Scholar | Crossref | |
|
Heger-Mahn, D., Warlimont, C., Faustmann, T., Gerlinger, C., Klipping, C.. 2004. “Combined Ethinylestradiol/Gestodene Contraceptive Patch: Two-center, Open-label Study of Ovulation Inhibition, Acceptability and Safety Over Two Cycles in Female Volunteers.” The European Journal of Contraception and Reproductive Health Care 9, no. 3: 173–81. Google Scholar | Crossref | Medline | |
|
Hoogland, H. J., Skouby, S. O.. 1993. “Ultrasound Evaluation of Ovarian Activity under Oral Contraceptives.” Contraception 47, no. 6: 583–90. Google Scholar | Crossref | |
|
Katkam, R. R., Gopalkrishnan, K., Chwalisz, K., Schillinger, E., Puri, C. P.. 1995. “Onapristone (ZK 98.299): A Potential Antiprogestin for Endometrial Contraception.” American Journal of Obstetrics and Gynecology 173 (3 Pt 1): 779–87. Google Scholar | Crossref | |
|
Katz, E. 1988. “The Luteinized Unruptured Follicle and Other Ovulatory Dysfunctions.” Fertility and Sterility 50, no. 6: 839–50. Google Scholar | Crossref | |
|
Kaur, R., Gupta, K.. 2016. “Endocrine Dysfunction and Recurrent Spontaneous Abortion: An Overview.” International Journal of Applied Basic Medical Research 6, no. 2: 79–83. Google Scholar | Crossref | |
|
Klipping, C., Duijkers, I., Remmers, A., Faustmann, T., Zurth, C., Klein, S., Shuett, B.. 2012. “Ovulation-inhibiting Effects of Dienogest in a Randomized, Dose-controlled Pharmacodynamic Trial of Healthy Women.” Journal of Clinical Pharmacology 52:1704–13. Google Scholar | Crossref | Medline | |
|
Klipping, C., Duijkers, I., Trummer, D., Marr, J.. 2008. “Suppression of Ovarian Activity with a Drospirenone-containing Oral Contraceptive in a 24/4 Regimen.” Contraception 78:16–25. Google Scholar | Crossref | Medline | |
|
Kroll, R., Seidman, L., Ricciotti, N., Howard, B., Weiss, H.. 2015. “A Phase 1, Multicentre, Open-label Study to Evaluate Ovarian Follicular Activity and Hormone Levels with an Extended-regimen Combined Oral Contraceptive with Low-dose Ethinyl Estradiol Supplementation.” The European Journal of Contraception & Reproductive Health Care 20, no. 4: 249–58. doi: 10.3109/13625187.2014.979282. Google Scholar | Crossref | |
|
Landgren, B. M., Unden, A. I., Diczfalusy, E.. 1980. “Hormonal Profile of the Cycle in 68 Normally Menstruating Women.” Acta Endocrinologica 94, no. 1: 89–96. Google Scholar | Crossref | |
|
Lawrenz, B., Humaidan, P., Kol, S., Fatemi, H.. 2018. “GnRHa Trigger and Luteal Coasting: A New Approach for the Ovarian Hyperstimulation Syndrome High-risk Patient?” Reproductive Biomedicine Online 36, no. 1: 75–77. doi: 10.1016/j.rbmo.2017.09.014. Google Scholar | Crossref | |
|
Liukkonen, S., Koskimies, A. I., Tenhunen, A., Ylöstalo, P.. 1984. “Diagnosis of Luteinized Unruptured Follicle (LUF) Syndrome by Ultrasound.” Fertility and Sterility 41, no. 1: 26–30. Google Scholar | Crossref | |
|
Ludicke, F., Sullivan, H., Spona, J., Elstein, M.. 2001. “Dose Finding in a Low-dose 21 Day Combined Oral Contraceptive Containing Gestodene.” Contraception 64, no. 4: 243–48. Google Scholar | Crossref | |
|
Medical Dictionary . 2012. “Medical Dictionary for the Health Professions and Nursing.” Accessed August 28, 2018. https://medical-dictionary.thefreedictionary.com/ovulation. Google Scholar | |
|
Ozlu, T., Gungor, A. C., Emine, M., Duran, D. B.. 2012. “Use of Progestogens in Pregnant and Infertile Patients.” Archives of Gynecology and Obstetrics 286, no. 2: 495–503. Google Scholar | Crossref | |
|
Pierson, R. A., Archer, D. F., Moreau, M., Shangold, G. A., Fisher, A. C., Creasy, G. W.. 2003. “Ortho Evra/Evra Versus Oral Contraceptives: Follicular Development and Ovulation in Normal Cycles and after an Intentional Dosing Error.” Fertility and Sterility 80, no. 1: 34–42. Google Scholar | Crossref | |
|
Puri, C. P., Katkam, R. R., Sachdeva, G., Patil, V., Manjramkar, D. D., Kholkute, S. D.. 2000. “Endometrial Contraception: Modulation of Molecular Determinants of Uterine Receptivity.” Steroids 65, no. 10–11: 783–94. Google Scholar | Crossref | Medline | |
|
Rossmanith, W., Steffens, D., Schramm, G.. 1997. “A Comarative Randomized Trial on the Impact of Two Low-dose Oral Contraceptives on Ovarian Activity, Cervical Permeability and Endometrial Receptivity.” Contraception 56:23–30. Google Scholar | Crossref | |
|
Rible, R. D., Taylor, D., Wilson, M., Stanczyk, F. Z., Mishell, D. R. 2009. “Follicular Development in a 7-day versus 4-day Hormone-free Interval with an Oral Contraceptive Containing 20 mcg Ethinyl Estradiol and 1 mg Norethindrone Acetate.” Contraception 79, no. 3: 182–88. Google Scholar | Crossref | |
|
Riesewijk, A., Martin, J., van Os, R., Horcajadas, J. A., Polman, J., Pellicer, A., Mosselman, S., Simon, C.. 2003. “Gene Expression Profiling of Human Endometrial Receptivity on Days LH+2 versus LH+7 by Microarray Technology.” Molecular Human Reproduction 9, no. 5: 253–64. Google Scholar | Crossref | Medline | |
|
Rivera, R., Yacobson, I., Grimes, D.. 1999. “The Mechanism of Action of Hormonal Contraceptives and Intrauterine Contraceptive Devices.” American Journal of Obstetrics and Gynecology 181 (5 Pt 1): 1263–69. Google Scholar | Crossref | Medline | |
|
Seidman, L., Kroll, R., Howard, B., Ricciotti, N., Hsieh, J., Weiss, H.. 2015. “Ovulatory Effects of Three Oral Contraceptive Regimens: A Randomized, Open-label, Descriptive Trial.” Contraception 91, no. 6: 495–502. doi: 10.1016/j.contraception.2015.03.001. Google Scholar | Crossref | |
|
Shaw, W. 1927. “Ovulation in the Human Ovary: Its Mechanism and Anomalies.” The Journal of Obstetrics and Gynecology of the British Empire 32, no. 3: 105–126. doi: 10.1111/j.1471-0528.1927.tb16004.x. Google Scholar | |
|
Spona, J., Binder, N., Hoschen, K., Feichtinger, W.. 2010. “Suppression of Ovarian Function by a Combined Oral Contraceptive Containing 0.02 mg Ethinyl Estradiol and 2 mg Chormadinone Acetate Given in a 24/4-day Intake Regimen over Three Cycles.” Fertility and Sterility 94, no. 4: 1195–201. Google Scholar | Crossref | |
|
Spona, J., Elstein, M., Feichtinger, W., Sullivan, H., Ludicke, F., Muller, U., Dusterberg, B.. 1996. “Shorter Pill Free Interval in Combined Oral Contraceptives Decreases Follicular Development.” Contraception 54:71–77. Google Scholar | Crossref | Medline | |
|
Spona, J., Feichtinger, W., Kindermann, C., Moore, C., Mellinger, U., Walter, F., Graser, T.. 1997. “Modulation of Ovarian Function by an Oral Contraceptive Containing 30 ug Ethinyl Estradiol in Comination with 2.00 mg Dienogest.” Contraception 56:185–91. Google Scholar | Crossref | |
|
Spona, J., Feichtinger, W., Kindermann, C., Wunsch, C., Brill, K.. 1996. “Inhibition of Ovulation by an Oral Contraceptive Containing 100 ug Levonorgestrel in Combination with 20 ug Ethinylestradiol.” Contraception 54:299–304. Google Scholar | Crossref | |
|
Stein, I. F., Leventhal, M. L.. 1935. “Amenorrhea Associated with Bilateral Polycystic Ovaries.” American Journal of Obstetrics and Gynecology 29, no. 2: 181–91. Google Scholar | Crossref | |
|
Tannus, S., Burke, Y., McCartney, C. R., Kol, S.. 2017. “GnRH-agonist Triggering for Final Oocyte Maturation in GnRH-antagonist IVF Cycles Induces Decreased LH Pulse Rate and Amplitude in Early Luteal Phase: A Possible Luteolysis Mechanism.” Gynecologic Endocrinology 33, no. 9: 741–45. Google Scholar | Crossref | |
|
Tavaniotou, A., Devroey, P.. 2003. “Effect of Human Chorionic Gonadotropin on Luteal Luteinizing Hormone Concentrations in Natural Cycles.” Fertility and Sterility 80, no. 3: 654–55. Google Scholar | Crossref | |
|
van der Does, J., Exalto, N., Dieben, T., Bennink, H.. 1995. “Ovarian Activity Suppression by Two Different Low-dose Triphasic Oral Contraceptives.” Contraception 52:357–61. Google Scholar | Crossref | |
|
van Heusden, A. M., Coelingh Bennink, H. J., Fauser, B. C.. 2002. “FSH and Ovarian Response: Spontaneous Recovery of Pituitary-ovarian Activity during the Pill-free Period vs. Exogenous Recombinant FDS during High Dose Combined Oral Contraceptives.” Clinical Endocrinology (Oxford) 56, no. 4: 509–17. Google Scholar | Crossref | |
|
Vigil, P., Lyon, C., Flores, B., Rioseco, H., Serrano, F.. 2017. “Ovulation, a Sign of Health.” Linacre Quarterly 84, no. 4: 343–55. Google Scholar | SAGE Journals | |
|
Waellnitz, K., Duijkers, I., Klipping, C., Rautenberg, T., Rohde, B., Zurth, C.. 2016. “A Two-centre, Open-label, Randomised Study of Ovulation Inhibition with Three Transdermal Contraceptive Patches, Each Containing Different Amounts of Ethinyl Estradiol and Gestodene in Healthy, Young Women.” Journal of Obstetrics and Gynaecology 36, no. 1: 106–13. doi: 10.3109/01443615.2015.1041882. Google Scholar | Crossref | |
|
Westhoff, C., Reinecke, I., Bangerter, K., Merz, M.. 2014. “Impact of Body Mass Index on Suppression of Follicular Development and Ovulation Using a Transdermal Patch Containing 0.55-mg Ethinyl Estradiol/2.1-mg Gestodene: A Multicenter, Open-label, Uncontrolled Study over Three Treatment Cycles.” Contraception 90:272–79. Google Scholar | Crossref | |
|
Westhoff, C. L., Torgal, A. H., Mayeda, E. R., Pike, M. C., Stanczyk, F. Z.. 2010. “Ovarian Suppresion in Normal-weight and Obese Women during Oral Contraceptive Use: A Randomized Controlled Trial.” Contraception 81, no. 6: 474–80. doi: 10.1016/j.contraception.2010.01.016. Epub February 20, 2010. Google Scholar | Crossref | Medline |
