What are the major parts of the female reproductive system?
There are a number of major parts that make up the female reproductive system:
- Ovaries: These two paired structures create the eggs (mature oocytes), which develop inside fluid-filled sacs called follicles. The ovaries releases eggs and have a hormonal function as well: making and secreting the hormones estrogen and progesterone, as well as smaller amounts of testosterone.i,ii
- Uterus: The embryo implants and develops in this hollow organ. It has two parts—the corpus (body) and cervix (bottom part of the uterus that is the path from the corpus to the vagina).iii A woman's uterus has three layers (from in to out):
- Endometrium: The inner uterine lining or cavity that is shed during menstruation. Its thickness varies by the time of the menstrual cycle in response to changes hormone levels.iv
- Myometrium: This thickest uterine layer, made up of smooth muscle, is the middle layer. It contracts to help sperm pass through the uterus to reach the egg. It also helps the embryo move into and along the uterus until implantation.v,vi
- Serosa: The outermost layer is a protective covering that prevents the uterus from sticking to neighboring organs.vii - Cervix: Although it is part of the uterus, the cervix is often thought of as its own entity. This tubular bottom part connects the uterus to the vagina, opening into the upper vaginal area. During natural conception, sperm passes from the vagina through the cervix into the uterus.viii
- Fallopian Tubes: These two tubes connect to the uterus, serving as a passageway between it and the ovaries. When eggs develop inside follicles and are released from the ovaries, they travel through the fallopian tubes and are fertilized there by the sperm. The fertilized egg then moves to the uterus and implants into the uterine wall.ix
- Vagina: The internal part of the female genitalia, this muscular, tubular structure connects the vulva to the cervix.x
- Vulva: This outer part of the female genitalia consists of the labia majora, labia minora, and clitoris.xi
What is the difference between a follicle and an oocyte?
- Oocytes develop inside cystic structures known as follicles. Primordial follicles (those at the earliest stage) develop at the beginning of each menstrual cycle. One becomes dominant, and the others arrest and do not develop further. The dominant follicle continues to develop until the oocyte inside it divides and develops into a mature oocyte, also known as an egg. During ovulation, the dominant follicle ruptures, releasing the egg to be caught by the fallopian tube.xii
In what phase of the menstrual cycle does conception occur?
Typically, a menstrual cycle ranges from 25 to 30 days. It includes both the ovarian cycle (pertaining to follicles in the ovaries) and the uterine cycle (dealing with endometrial changes).xiii
The ovarian cycle has two phases: follicular and luteal. The follicular phase can vary in length, while the luteal phase is more consistent and typically lasts around 14 days.xiv
- Follicular phase: This phase starts with the onset of menstrual bleeding, when the endometrial lining is shed. The phase lasts throughout menstruation and ends at ovulation. Ovulation occurs 10-12 hours after the peak of the luteinizing hormone (LH) surge and 34-36 hours after the start of the LH surge starts.xv
- Luteal phase: This phase starts after ovulation and ends when menstruation occurs or when conception takes place. If fertilization occurs, this happens during the luteal phase, after ovulation.xvi
After ovulation, the mature oocyte (or egg) enters the fallopian tube. The egg will stay inside the fallopian tube and can survive for about 24 hours. This is the window when conception or fertilization most often occurs. In natural conception, sperm travel up the cervix, into the uterus, and up into the fallopian tubes. A sperm may meet one of the ovulated eggs in the fallopian tube and fertilization may occur.xvii
The fertilized egg is now an early-stage embryo (zygote). It slowly passes through the fallopian tube for 3-4 days, eventually reaching the uterus. The embryo (now a group of cells called a blastocyst or day 5 or 6 embryo) drops into the uterus where it must implant into the lining of the uterus to continue developing.xviii
When is the fertile window?
This window is the time during which fertilization (conception) can occur.xix
What is occurring anatomically during the fertile window?
The egg must be exposed to a sperm during this time for fertilization to occur.xx Sperm can survive in a woman's reproductive tract for up to five days,xxi,xxii but the average lifespan is 1.4 days.xxiii Because sperm have a potential 5-day survival and the egg stays in the fallopian tube for up to 24 hours, the fertile window can span from five days before ovulation to one day after.xxiv
This creates an approximately six-day window for an egg to be fertilized and for getting pregnant. On average, the fertile window is from day 8 to day 14 of the menstrual cycle.xxv
What are hormones doing during the fertile window?
Roughly three days before ovulation, estradiol rises to peak levels, indicating the start of the fertile window.xxvi This rise eventually triggers the LH surge (a large amount of LH released from the pituitary gland) which takes approximately 24 hours. At the same time, a smaller follicle-stimulating hormone (FSH) surge occurs.xxvii Ovulation occurs 34-36 hours after the LH surge starts and sharply declines once the surge is over.xxviii
When the LH surge starts, estradiol slowly declines until after ovulation, after which it begins to increase again, until immediately before menstruation, when it declines again.xxix Progesterone, which is low during the fertile window, also rises during the LH surge and peaks about 7 days after ovulation.xxx
How does an ovulation predictor kit (OPK) work?
OPKs (Ovulation Predictor Kits) are urine tests that are used to indicate the fertile window. Some measure LH only, and others measure both LH and estrogen metabolites (estrone-3-glucuronide or E3G) found in urine.xxxi,xxxii,xxxiii,xxxiv,xxxv,xxxvi,xxxvii These kits cannot definitively determine when ovulation will occur, but they give individuals pursuing conception a good idea of ovulation timing. Typically, ovulation occurs roughly 36 hours (between 24-48 hours) after the LH surge starts.xxxviii
It is worth noting that some women will have an LH surge but will not release an egg. In these cases, OPKs will indicate the surge, but ovulation will not follow.xxxix There is also a chance for a false positive result on home OPK. Because of this, some providers may confirm a positive OPK with an office blood test or ultrasound if OPKs are being used to time intrauterine insemination (IUI) or for women with infertility. OPKs that measure both LH and E3G may help pinpoint the window's start, potentially indicated by an estrogen rise. This elevation typically occurs 3 days before the LH surge. Consequently, these OPKs may identify the window a few days before LH-only kits.xl
What happens if you have sex during the fertile window?
During the window, with unassisted conception, semen (containing sperm) is ejaculated into the vagina. Within 5-10 minutes, the sperm can travel through the cervix into the uterus and fallopian tubes.xli,xlii Once there, if a sperm meets an egg, fertilization may occur.
What role does age play when trying to conceive?
While the sperm plays a significant role in fertilization, the chance of conception for individuals who are trying to conceive (TTC) unassisted varies with the woman's age (i.e., the age of the egg). The chart below shows conception rates for three age groups. The data comes from a cohort study of 2 962 couples in the United States and Canada who had been trying to conceive naturally for less than three menstrual cycles. Although not included in the table, it should be noted that the cumulative pregnancy rate after six cycles for women aged 40-45 was 55 percent lower than women aged 28-30.xliii
Table 1. The cumulative pregnancy rates by female age, after 6 cycles, and after 12 cycles in over 2 900 heterosexual couples trying to conceive naturally (at home).*
*Wesselink, A. K., et al. (2017). Age and fecundability in a North American preconception cohort study. American Journal of Obstetrics and Gynecology, 217(6), 667.e1-667.e8. https://doi.org/10.1016/j.ajog.2017.09.002
Sperm’s role
Each ejaculation contains 1.5-5mL of semen—and between 200-500 million sperm.xliv After intercourse, the semen pools in the vagina near the opening of the cervix, called the cervical os.xlv While only one sperm is needed for fertilization, having a high number is critical because not all sperm will be viable, and they face several obstacles on the journey to the egg. First, sperm must overcome the vagina’s naturally low pH. While sperm's ideal environment is between 7.0 and 8.5 pH (more basic or alkaline), the normal vagina is more acidic, ranging between a pH of 3.5 to 4.xlvi,xlvii
Fortunately, both seminal fluid and cervical mucus are more alkaline, counteracting the vagina’s pH and allowing sperm to survive.xlviii One study from the 1970s shows that the interaction between the seminal fluid and the vagina raises the vagina’s pH to 7 after ejaculation, creating a good environment in which sperm can survive.xlix
Immediately after ejaculation, the seminal fluid coagulates and becomes jelly-like. This keeps the sperm inside the vagina near the cervix and protects the sperm from an acidic vaginal environment. Sperm begin to exit the coagulated semen immediately and pass through the cervix, with some sperm reaching the fallopian tubes within 5-10 minutes. Substances in the semen gradually liquify the coagulated semen in the vagina, and within 30 minutes, sperm remaining in the vagina have reduced motility because of exposure to the acidic vaginal environment. After about 1 hour, the remaining semen is entirely liquid and typically flows out of the vagina with the remaining non-motile sperm.l,li
Once the sperm reach and enter the cervix, the pH is higher and therefore more hospitable. During ovulation, the pH of the cervix is even better for sperm survival, facilitating sperm entry and fertilization.lii After sperm travel past the cervix, it is thought that uterine contractions assist the sperm in passing through the uterus and to the fallopian tubes.liii Fluid in the tubes, which increases during ovulation, helps propel the sperm forward to help them get to the egg.liv
There are some barriers along the way. For example, some sperm, particularly those with abnormal structure, may struggle to pass through the cervical mucous or fallopian tubes.lv,lvi Ultimately, millions of sperm enter the uterus, but studies show only a few hundred make it to the fallopian tubes.lvii
Fertilization and the early embryo
A process called capacitation is required before ejaculated sperm can fertilize an egg. Capacitation is a series of changes to the structure of the sperm as it moves from the cervix to the egg’s location in the fallopian tube; these changes include the sperm developing special receptors that guide it to the egg’s outer layer. Capacitation also stops sperm with poor motility or morphology from reaching the egg. It is believed features of the female reproductive tract (such as exposure to cervical mucus) trigger capacitation.lviii,lix,lx,lxi,lxii,lxiii
The acrosome reaction is the last step for sperm before they are ready for fertilization. Once the sperm reaches the egg’s outer shell, known as the zona pellucida, the cap over the sperm’s head (acrosome) releases chemicals. This reaction helps the sperm break through the zona pellucida.lxiv,lxv It takes roughly 5-20 minutes for the sperm to break through and fuse to the plasma membrane inside of the egg. Once complete, the zygote (the earliest embryo stage) forms, and fertilization has occurred.lxvi
The zygote now thickens and strengthens the zona pellucida, preventing penetration by any other sperm.lxvii Within 1-3 minutes of fusing with the plasma membrane, the sperm loses motility and is essentially frozen.lxviii
As the zygote moves down the fallopian tubes toward the uterus, it divides along the way. The single-celled zygote divides into 2 cells and then 4 cells. By day 3, it is 8 cells. On day 4, it is a compacted ball of cells called a morula, and by this point it has typically reached the end of the fallopian tube and drops into the uterus. Once in the uterus, the embryo continues to divide, becoming a blastocyst on day 5 or 6.lxix At this point, the blastocyst hatches out of the protective zona pellucida.lxx
What is implantation?
The process called implantation occurs when the embryo attaches to the endometrium where it stays throughout pregnancy. The upper and back walls of the uterus are common implantation locations.lxxi
For implantation to occur, the endometrium must be receptive and have adequate thickness. Thickness varies based on the day of the menstrual cycle and from person to person. Typically, the endometrium thickens to a peak level around ovulation to prepare for implantation. Ultimately, before the embryo implants, it must reach the uterus when the endometrium is suitable for implantation with adequate nutrients.lxxii,lxxiii
Two parts of the blastocyst will continue to develop—the inner cell mass (which will develop into the embryo) and the trophoblast (which develops into the placenta). The trophoblast attaches to the receptive endometrium.lxxiv,lxxv,lxxvi
Implantation is an essential part of pregnancy. The uterine lining provides the initial nutrients required by the developing fetus until the placenta takes over. Through implantation, the growing embryo gets enough sustenance to continue developing.lxxvii
Some women do have symptoms with implantation. The most common are light bleeding, spotting, or cramping pain. This can sometimes be confused with the onset of menstruation, but these symptoms generally last for a shorter period of time, on average less than 3 days.lxxviii,lxxix,lxxx Roughly 25 percent of women have vaginal bleeding during the first trimester. It can coincide with implantation or occur after.lxxxi
In an estimated 1 to 2% of caseslxxxii,lxxxiii, fertilization occurs but the zygote implants somewhere other than in the uterus, typically in the fallopian tube. This is called an “ectopic pregnancy.”lxxxiv,lxxxv This type of pregnancy is not viable and is typically terminated (using medication or surgery) as allowing the embryo to grow outside the uterus can lead to severe medical complications in the woman including death.lxxxvi
What happens if there is no implantation?
If fertilization does not occur or an embryo fails to implant, estrogen and progesterone levels drop steeply around day 28 of the menstrual cycle. Because these hormones support the uterine lining, when they decrease, the uterine lining sheds (menstrual bleeding). Any embryo that fails to implant will be reabsorbed by the tissues or passed out of the cervix with menstrual blood.
Women typically experience no symptoms if a blastocyst does not implant or stops developing immediately after implantation and is shed with the next period. In many instances, they are unaware there was a fertilized egg and that they were pregnant during these early days. The only sign of a biochemical pregnancy could be a positive at-home pregnancy test that detects the pregnancy hormone (human chorionic gonadotropin, hCG) that is followed a few days later by a negative pregnancy test or the onset of a menstrual period.
Conclusion
With these fundamentals, individuals seeking a healthy pregnancy will have a better understanding of the process of conception. Reviewing this information for educational purposes before consulting a physician can help individuals better absorb the advice, diagnosis, or treatment that is offered by the fertility specialist.
i Rosner, J., et al. (2021). Physiology, Female Reproduction. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK537132/
ii Saei Ghare Naz, M., et al. (2020). The menstrual disturbances in endocrine disorders: A narrative review. International Journal of Endocrinology and Metabolism, 18(4). https://doi.org/10.5812/ijem.106694
iii Rosner, J., et al. (2021). Physiology, Female Reproduction. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK537132/
iv Rosner, J., et al. (2021). Physiology, Female Reproduction. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK537132/
v Rosner, J., et al. (2021). Physiology, Female Reproduction. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK537132/
vi Lessey, B. A., & Young, S. L. (2014). The structure, function, and evaluation of the female reproductive tract. Yen & Jaffe's Reproductive Endocrinology, 192-235.e16. https://doi.org/10.1016/b978-1-4557-2758-2.00010-x
vii University of Rochester Medical Center, H. (n.d.). Anatomy of the uterus - Health encyclopedia. https://www.urmc.rochester.edu/encyclopedia/content.aspx?ContentTypeID=34&ContentID=17114-1
viii Rosner, J., et al. (2021). Physiology, Female Reproduction. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK537132/
ix Rosner, J., et al. (2021). Physiology, Female Reproduction. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK537132/
x Rosner, J., et al. (2021). Physiology, Female Reproduction. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK537132/
xi Rosner, J., et al. (2021). Physiology, Female Reproduction. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK537132/
xii Arroyo, A., et al. (2020). Luteinizing hormone action in human oocyte maturation and quality: Signaling pathways, regulation, and clinical impact. Reproductive Sciences, 27(6), 1223-1252. https://doi.org/10.1007/s43032-019-00137-x
xiii Bull, J. R., et al. (2019). Real-world menstrual cycle characteristics of more than 600,000 menstrual cycles. npj Digital Medicine, 2(1). https://doi.org/10.1038/s41746-019-0152-7
xiv Reed, B. G., & Carr, B. R. (2018). The Normal Menstrual Cycle and the Control of Ovulation. Endotext. https://www.ncbi.nlm.nih.gov/books/NBK279054/
xv Reed, B. G., & Carr, B. R. (2018). The Normal Menstrual Cycle and the Control of Ovulation. Endotext. https://www.ncbi.nlm.nih.gov/books/NBK279054/
xvi Reed, B. G., & Carr, B. R. (2018). The Normal Menstrual Cycle and the Control of Ovulation. Endotext. https://www.ncbi.nlm.nih.gov/books/NBK279054/
xvii Niakan, K. K., et al. (2012). Human pre-implantation embryo development. Development, 139(5), 829-841. https://doi.org/10.1242/dev.060426
xviii Niakan, K. K., et al. (2012). Human pre-implantation embryo development. Development, 139(5), 829-841. https://doi.org/10.1242/dev.060426
xix Wilcox, A. J. (2000). The timing of the "Fertile window" in the menstrual cycle: Day specific estimates from a prospective study. BMJ, 321(7271), 1259-1262. https://doi.org/10.1136/bmj.321.7271.1259
xx Reed, B. G., & Carr, B. R. (2018). The Normal Menstrual Cycle and the Control of Ovulation. Endotext. https://www.ncbi.nlm.nih.gov/books/NBK279054/
xxi Orr, T. J., & Brennan, P. L. (2015). Sperm storage: Distinguishing selective processes and evaluating criteria. Trends in Ecology & Evolution, 30(5), 261-272. https://doi.org/10.1016/j.tree.2015.03.006
xxii Suarez, S., & Pacey, A. A. (2005). Sperm transport in the female reproductive tract. Human Reproduction Update, 12(1), 23-37. https://doi.org/10.1093/humupd/dmi047
xxiii Weinberg, C. R., & Wilcox, A. J. (1995). A model for estimating the potency and survival of human gametes in vivo. Biometrics, 51(2), 405. https://doi.org/10.2307/2532929
xxiv Stanford, J. B. (2015). Revisiting the Fertile window. Fertility and Sterility, 103(5), 1152-1153. https://doi.org/10.1016/j.fertnstert.2015.02.015
xxv Direito, A., et al. (2013). Relationships between the luteinizing hormone surge and other characteristics of the menstrual cycle in normally ovulating women. Fertility and Sterility, 99(1), 279-285.e3. https://doi.org/10.1016/j.fertnstert.2012.08.047
xxvi Direito, A., et al. (2013). Relationships between the luteinizing hormone surge and other characteristics of the menstrual cycle in normally ovulating women. Fertility and Sterility, 99(1), 279-285.e3. https://doi.org/10.1016/j.fertnstert.2012.08.047
xxvii Direito, A., et al. (2013). Relationships between the luteinizing hormone surge and other characteristics of the menstrual cycle in normally ovulating women. Fertility and Sterility, 99(1), 279-285.e3. https://doi.org/10.1016/j.fertnstert.2012.08.047
xxviii Reed, B. G., & Carr, B. R. (2018). The Normal Menstrual Cycle and the Control of Ovulation. Endotext. https://www.ncbi.nlm.nih.gov/books/NBK279054/
xxix Reed, B. G., & Carr, B. R. (2018). The Normal Menstrual Cycle and the Control of Ovulation. Endotext. https://www.ncbi.nlm.nih.gov/books/NBK279054/
xxx Reed, B. G., & Carr, B. R. (2018). The Normal Menstrual Cycle and the Control of Ovulation. Endotext. https://www.ncbi.nlm.nih.gov/books/NBK279054/
xxxi Leiva, R., et al. (2014). Use of ovulation predictor kits as adjuncts when using fertility awareness methods (FAMs): A pilot study. The Journal of the American Board of Family Medicine, 27(3), 427-429. https://doi.org/10.3122/jabfm.2014.03.130255
xxxii Manders, M., et al. (2014). Timed intercourse for couples trying to conceive. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.cd011345
xxxiii American Pregnancy Association. (2021). How to use ovulation kits & fertility monitors. https://americanpregnancy.org/getting-pregnant/ovulation-kits/
xxxiv Clearblue. (2021). Advanced Digital Ovulation Test. https://www.clearblue.com/ovulation-tests/advanced-digital
xxxv Clearblue. (2021). Digital Ovulation Test. https://www.clearblue.com/ovulation-tests/digital
xxxvi First Response. (n.d.). Easy read ovulation test. https://www.firstresponse.com/en-ca/products/ovulation/easy-read-ovulation-test
xxxvii Soumpasis, I., et al. (2020). Real-life insights on menstrual cycles and ovulation using big data. Human Reproduction Open, 2020(2). https://doi.org/10.1093/hropen/hoaa011
xxxviii Soumpasis, I., et al. (2020). Real-life insights on menstrual cycles and ovulation using big data. Human Reproduction Open, 2020(2). https://doi.org/10.1093/hropen/hoaa011
xxxix Soumpasis, I., et al. (2020). Real-life insights on menstrual cycles and ovulation using big data. Human Reproduction Open, 2020(2). https://doi.org/10.1093/hropen/hoaa011
xl Johnson, S., et al. (2015). Development of the first urinary reproductive hormone ranges referenced to independently determined ovulation day. Clinical Chemistry and Laboratory Medicine (CCLM), 53(7). https://doi.org/10.1515/cclm-2014-1087
xli Carlson, B. M. (2018). The human body: Linking structure and function. Academic Press. https://doi.org/10.1016/B978-0-12-804254-0.00014-4
xlii Soumpasis, I., et al. (2020). Real-life insights on menstrual cycles and ovulation using big data. Human Reproduction Open, 2020(2). https://doi.org/10.1093/hropen/hoaa011
xliii Wesselink, A. K., et al. (2017). Age and fecundability in a North American preconception cohort study. American Journal of Obstetrics and Gynecology, 217(6), 667.e1-667.e8. https://doi.org/10.1016/j.ajog.2017.09.002
xliv Brannigan, R. E., & Lipshultz, L. I. (2009). Sperm transport and capacitation. The Global Library of Women's Medicine. https://doi.org/10.3843/glowm.10316
xlv Suarez, S., & Pacey, A. A. (2005). Sperm transport in the female reproductive tract. Human Reproduction Update, 12(1), 23-37. https://doi.org/10.1093/humupd/dmi047
xlvi Makler, A., et al. (1981). Factors affecting sperm motility. vii. sperm viability as affected by change of pH and osmolarity of semen and urine specimens. Fertility and Sterility, 36(4), 507-511. https://doi.org/10.1016/s0015-0282(16)45802-4
xlvii Peek, J. C., & Matthews, C. D. (1986). The pH of cervical mucus, quality of semen, and outcome of the post-coital test. Clinical reproduction and fertility, 4(3), 217–225.
xlviii Brannigan, R. E., & Lipshultz, L. I. (2009). Sperm transport and capacitation. The Global Library of Women's Medicine. https://doi.org/10.3843/glowm.10316
xlix Fox, C. A., et al. (1973). Continuous measurement by radio-telemetry of vaginal pH during human coitus. Reproduction, 33(1), 69-75. https://doi.org/10.1530/jrf.0.0330069
l Brannigan, R. E., & Lipshultz, L. I. (2009). Sperm transport and capacitation. The Global Library of Women's Medicine. https://doi.org/10.3843/glowm.10316
li Suarez, S., Pacey, A., “Sperm transport in the female reproductive tract.“ Human Reproduction Update. 12(1):23-37. https://doi.org/10.1093/humupd/dmi047
lii Wolf, D. P., et al. (1978). Human cervical mucus. IV. Viscoelasticity and sperm penetrability during the Ovulatory menstrual Cycle**Supported by national institutes of health contract NO1-HD-4-2838. Fertility and Sterility, 30(2), 163-169. https://doi.org/10.1016/s0015-0282(16)43454-0
liii Kunz, G., et al. (1996). The dynamics of rapid sperm transport through the female genital tract: Evidence from vaginal sonography of uterine peristalsis and hysterosalpingoscintigraphy. Human Reproduction, 11(3), 627-632. https://doi.org/10.1093/humrep/11.3.627
liv Brannigan, R. E., & Lipshultz, L. I. (2009). Sperm transport and capacitation. The Global Library of Women's Medicine. https://doi.org/10.3843/glowm.10316
lv Qu, Y., et al. (2020). Cooperation-based sperm clusters mediate sperm oviduct entry and fertilization. https://doi.org/10.1101/2020.10.18.344275
lvi Saint-Dizier, M., et al. (2020). Sperm interactions with the female reproductive tract: A key for successful fertilization in mammals. Molecular and Cellular Endocrinology, 516, 110956. https://doi.org/10.1016/j.mce.2020.110956
lvii Williams, M., et al. (1993). Physiology: Sperm numbers and distribution within the human fallopian tube around ovulation. Human Reproduction, 8(12), 2019-2026. https://doi.org/10.1093/oxfordjournals.humrep.a137975
lviii De Jonge, C. (2017). Biological basis for human capacitation—revisited. Human Reproduction Update. https://doi.org/10.1093/humupd/dmw048
lix Brannigan, R. E., & Lipshultz, L. I. (2009). Sperm transport and capacitation. The Global Library of Women's Medicine. https://doi.org/10.3843/glowm.10316
lx Overstreet, J. W., et al. (1991). Cervical mucus and sperm transport in reproduction. Seminars in perinatology, 15(2), 149–155.
lxi Stival, C., et al. (2016). Sperm capacitation and acrosome reaction in mammalian sperm. Sperm Acrosome Biogenesis and Function During Fertilization, 93-106. https://doi.org/10.1007/978-3-319-30567-7_5
lxii Puga Molina, L. C., et al. (2018). CFTR/enac-dependent regulation of membrane potential during human sperm capacitation is initiated by bicarbonate uptake through NBC. Journal of Biological Chemistry, 293(25), 9924-9936. https://doi.org/10.1074/jbc.ra118.003166
lxiii Castillo, J., et al. (2019). Proteomic changes in human sperm during sequential in vitro capacitation and acrosome reaction. Frontiers in Cell and Developmental Biology, 7. https://doi.org/10.3389/fcell.2019.00295
lxiv Crozet N. (1994). Réaction acrosomique et fécondation [Acrosome reaction and fertilization]. Contraception, fertilite, sexualite (1992), 22(5), 328–330.
lxv Castillo, J., et al. (2019). Proteomic changes in human sperm during sequential in vitro capacitation and acrosome reaction. Frontiers in Cell and Developmental Biology, 7. https://doi.org/10.3389/fcell.2019.00295
lxvi Cole, L. A. (2016). Sperm activation, fertilization, morula, blastocyst formation, and twinning. Biology of Life, 143-150. https://doi.org/10.1016/b978-0-12-809685-7.00019-8
lxvii Cole, L. A. (2016). Sperm activation, fertilization, morula, blastocyst formation, and twinning. Biology of Life, 143-150. https://doi.org/10.1016/b978-0-12-809685-7.00019-8
lxviii Cole, L. A. (2016). Sperm activation, fertilization, morula, blastocyst formation, and twinning. Biology of Life, 143-150. https://doi.org/10.1016/b978-0-12-809685-7.00019-8
lxix Niakan, K. K., et al. (2012). Human pre-implantation embryo development. Development, 139(5), 829-841. https://doi.org/10.1242/dev.060426
lxx Niakan, K. K., et al. (2012). Human pre-implantation embryo development. Development, 139(5), 829-841. https://doi.org/10.1242/dev.060426
lxxi Kim, S., & Kim, J. (2017). A review of mechanisms of implantation. Development & Reproduction, 21(4), 351-359. https://doi.org/10.12717/dr.2017.21.4.351
lxxii Kim, S., & Kim, J. (2017). A review of mechanisms of implantation. Development & Reproduction, 21(4), 351-359. https://doi.org/10.12717/dr.2017.21.4.351
lxxiii Wolter, J. (2013). The process of implantation of embryos in primates. The Embryo Project Encyclopedia. https://embryo.asu.edu/pages/process-implantation-embryos-primates
lxxiv Wolter, J. (2013). The process of implantation of embryos in primates. The Embryo Project Encyclopedia. https://embryo.asu.edu/pages/process-implantation-embryos-primates
lxxv Kim, S., & Kim, J. (2017). A review of mechanisms of implantation. Development & Reproduction, 21(4), 351-359. https://doi.org/10.12717/dr.2017.21.4.351
lxxvi Kumar, P., & Sharma, A. (2012). Understanding implantation window, a crucial phenomenon. Journal of Human Reproductive Sciences, 5(1), 2. https://doi.org/10.4103/0974-1208.97777
lxxvii Coughlan, C., et al. (2014). Recurrent implantation failure: Definition and management. Reproductive BioMedicine Online, 28(1), 14-38. https://doi.org/10.1016/j.rbmo.2013.08.011
lxxviii Sapra, K., et al. (2016). Signs and symptoms associated with early pregnancy loss: Findings from a population-based preconception cohort. Human Reproduction, 31(4), 887-896. https://doi.org/10.1093/humrep/dew010
lxxix Li D., et al. (2003). Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study. BMJ, 327-368. https://doi.org/10.1136/bmj.327.7411.368
lxxx Hasan, R., et al. (2010). Patterns and predictors of vaginal bleeding in the first trimester of pregnancy. Annals of Epidemiology, 20(7), 524-531. https://doi.org/10.1016/j.annepidem.2010.02.006
lxxxi Hasan, R., et al. (2010). Patterns and predictors of vaginal bleeding in the first trimester of pregnancy. Annals of Epidemiology, 20(7), 524-531. https://doi.org/10.1016/j.annepidem.2010.02.006
lxxxii Creanga, A. A., et al. (2011). Trends in ectopic pregnancy mortality in the United States. Obstetrics & Gynecology, 117(4), 837-843. https://doi.org/10.1097/aog.0b013e3182113c10
lxxxiii Marion, L. L., & Meeks, G. R. (2012). Ectopic pregnancy. Clinical Obstetrics & Gynecology, 55(2), 376-386. https://doi.org/10.1097/grf.0b013e3182516d7b
lxxxiv Hendriks, E., et al. (2020). Ectopic Pregnancy: Diagnosis and Management. American family physician, 101(10), 599–606.
lxxxv Li, C., et al. (2015). Risk factors for ectopic pregnancy: A multi-center case-control study. BMC Pregnancy and Childbirth, 15(1). https://doi.org/10.1186/s12884-015-0613-1
lxxxvi Creanga, A. A., et al. (2011). Trends in ectopic pregnancy mortality in the United States. Obstetrics & Gynecology, 117(4), 837-843. https://doi.org/10.1097/aog.0b013e3182113c10