Ovarian stimulation
Encyclopedia
Ovarian hyperstimulation (also called controlled ovarian hyperstimulation) is where a regimen of fertility medications are used to stimulate the development of multiple follicles
of the ovaries in one single cycle, resulting in superovulation (release of a larger-than-normal number of eggs). It may be used as a part of in vitro fertilization. Treatment cycles are typically started on the third day of menstruation
.
In contrast, when referring to the reversal of oligoovulation or anovulation
, the preferred term is rather ovulation induction
.
s are used, usually FSH analogues. A meta-analysis came to the result that the optimal daily recombinant FSH stimulation dose is 150 IU/day in presumed normal responders younger than 39 years undergoing IVF. Compared with higher doses, this dose is associated with a slightly lower oocyte yield, but similar pregnancy rate
s and embryo cryopreservation rates. There is a concomitant monitoring, including frequently checking the estradiol
level and, by means of gynecologic ultrasonography
, follicular growth. Typically approximately 10 days of injections will be necessary. Concomitantly administering recombinant hCG
has no significant beneficial effect. Spontaneous ovulation during the cycle is typically prevented by the use of GnRH
agonists or GnRH antagonists, which block the natural surge of luteinising hormone (LH).
is conventionally used. Automated follicle tracking does not appear to improve the clinical outcome of assisted reproduction treatment.
using human chorionic gonadotropin
(hCG). hCH makes the follicles perform their final maturation. A transvaginal oocyte retrieval
is then performed just prior to when the follicles would rupture. Alternatively, coasting may be performed, which is ovarian hyperstimulation in IVF without hCG administration. Coasting radically decreases the risk of ovarian hyperstimulation syndrome
(OHSS), with a study of high risk patients showing no incidence of OHSS in 21 patients, versus ~20% in the control group. On the other hand, live birth rate may be slightly decreased, with the same study resulting in 38% in coasting vs. 45% among controls, as well as decreased cumulative live birth rate (52% vs. 59%), presumably because of more difficulty in timing oocyte retrieval with full maturation. However, there appears to be no significantly decreased birth rate among high responder patients, in the associated study defined as those having at least 20 follicles, each measuring ≥10 mm in diameter with ≥20% of them of diameter ≥15 mm.
Patients may be classified by response as low responders, normal or average responders or high responders.
is letting ovarian follicle
s mature in vitro
, and with this technique ovarian hyperstimulation isn't essential. Rather, oocytes can mature outside the body prior to IVF. Hence, no (or at least a lower dose of) gonadotropins have to be injected in the body. However, there still isn't enough evidence to prove the effectiveness and security of the technique.
Ovarian follicle
Ovarian follicles are the basic units of female reproductive biology, each of which is composed of roughly spherical aggregations of cells found in the ovary. They contain a single oocyte . These structures are periodically initiated to grow and develop, culminating in ovulation of usually a single...
of the ovaries in one single cycle, resulting in superovulation (release of a larger-than-normal number of eggs). It may be used as a part of in vitro fertilization. Treatment cycles are typically started on the third day of menstruation
Menstruation
Menstruation is the shedding of the uterine lining . It occurs on a regular basis in sexually reproductive-age females of certain mammal species. This article focuses on human menstruation.-Overview:...
.
In contrast, when referring to the reversal of oligoovulation or anovulation
Anovulation
An anovulatory cycle is a menstrual cycle during which the ovaries do not release an oocyte. Therefore, ovulation does not take place. However, a woman who does not ovulate at each menstrual cycle is not necessarily going through menopause...
, the preferred term is rather ovulation induction
Ovulation induction
Ovulation induction is the stimulation of ovulation by medication. It is usually used in the sense of stimulation of the development of ovarian follicles to reverse anovulation or oligoovulation, but can also be used in the sense of triggering oocyte release from relatively mature ovarian follicles...
.
Medications used
In most patients injectable gonadotropinGonadotropin
Gonadotropins are protein hormones secreted by gonadotrope cells of the pituitary gland of vertebrates. This is a family of proteins, which include the mammalian hormones follitropin , lutropin , placental chorionic gonadotropins hCG and eCG and chorionic gonadotropin , as well as at least two...
s are used, usually FSH analogues. A meta-analysis came to the result that the optimal daily recombinant FSH stimulation dose is 150 IU/day in presumed normal responders younger than 39 years undergoing IVF. Compared with higher doses, this dose is associated with a slightly lower oocyte yield, but similar pregnancy rate
Pregnancy rate
Pregnancy rate in infertility treatment is the success rate for pregnancy. It is the percentage of all attempts that leads to pregnancy, with attempts generally referring to menstrual cycles where insemination or any artificial equivalent is used, which may be simple artificial insemination or AI...
s and embryo cryopreservation rates. There is a concomitant monitoring, including frequently checking the estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
level and, by means of gynecologic ultrasonography
Gynecologic ultrasonography
Gynecologic ultrasonography or Gynecologic sonography refers to the application of medical ultrasonography to the female pelvic organs, specifically the uterus, the ovaries, the Fallopian tubes, as well as the bladder, the adnexa, the Pouch of Douglas, and any findings in the pelvis of relevance...
, follicular growth. Typically approximately 10 days of injections will be necessary. Concomitantly administering recombinant hCG
Human chorionic gonadotropin
Human chorionic gonadotropin or human chorionic gonadotrophin is a glycoprotein hormone produced during pregnancy that is made by the developing embryo after conception and later by the syncytiotrophoblast .. Some tumors make this hormone; measured elevated levels when the patient is not...
has no significant beneficial effect. Spontaneous ovulation during the cycle is typically prevented by the use of GnRH
Gonadotropin-releasing hormone
Gonadotropin-releasing hormone , also known as Luteinizing-hormone-releasing hormone and luliberin, is a tropic peptide hormone responsible for the release of follicle-stimulating hormone and luteinizing hormone from the anterior pituitary. GnRH is synthesized and released from neurons within...
agonists or GnRH antagonists, which block the natural surge of luteinising hormone (LH).
Tracking
Tracking or supervising the maturation of follicles is performed in order to timely schedule oocyte retrieval. Two-dimensional ultrasoundGynecologic ultrasonography
Gynecologic ultrasonography or Gynecologic sonography refers to the application of medical ultrasonography to the female pelvic organs, specifically the uterus, the ovaries, the Fallopian tubes, as well as the bladder, the adnexa, the Pouch of Douglas, and any findings in the pelvis of relevance...
is conventionally used. Automated follicle tracking does not appear to improve the clinical outcome of assisted reproduction treatment.
Retrieval
When used in conjunction with in vitro fertilization (IVF), ovarian hyperstimulation may be followed by ovulation inductionOvulation induction
Ovulation induction is the stimulation of ovulation by medication. It is usually used in the sense of stimulation of the development of ovarian follicles to reverse anovulation or oligoovulation, but can also be used in the sense of triggering oocyte release from relatively mature ovarian follicles...
using human chorionic gonadotropin
Human chorionic gonadotropin
Human chorionic gonadotropin or human chorionic gonadotrophin is a glycoprotein hormone produced during pregnancy that is made by the developing embryo after conception and later by the syncytiotrophoblast .. Some tumors make this hormone; measured elevated levels when the patient is not...
(hCG). hCH makes the follicles perform their final maturation. A transvaginal oocyte retrieval
Transvaginal oocyte retrieval
Transvaginal oocyte retrieval , also referred to as oocyte retrieval or even simply egg collection, is a technique used in in vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body...
is then performed just prior to when the follicles would rupture. Alternatively, coasting may be performed, which is ovarian hyperstimulation in IVF without hCG administration. Coasting radically decreases the risk of ovarian hyperstimulation syndrome
Ovarian hyperstimulation syndrome
Ovarian hyperstimulation syndrome is a complication from some forms of fertility medication. Most cases are mild, but a small proportion are severe.-Causative medications:...
(OHSS), with a study of high risk patients showing no incidence of OHSS in 21 patients, versus ~20% in the control group. On the other hand, live birth rate may be slightly decreased, with the same study resulting in 38% in coasting vs. 45% among controls, as well as decreased cumulative live birth rate (52% vs. 59%), presumably because of more difficulty in timing oocyte retrieval with full maturation. However, there appears to be no significantly decreased birth rate among high responder patients, in the associated study defined as those having at least 20 follicles, each measuring ≥10 mm in diameter with ≥20% of them of diameter ≥15 mm.
Antral follicle count
The response to gonadotropins may be roughly approximated by antral follicle count (AFC), estimated by vaginal ultrasound, which in turn reflects how many primordial follicles there are in reserve in the ovary.Patients may be classified by response as low responders, normal or average responders or high responders.
| Antral follicle count | Classification | Approximate expected response | Risks | Pregnancy rate Pregnancy rate Pregnancy rate in infertility treatment is the success rate for pregnancy. It is the percentage of all attempts that leads to pregnancy, with attempts generally referring to menstrual cycles where insemination or any artificial equivalent is used, which may be simple artificial insemination or AI... s | Recommendation |
|---|---|---|---|---|---|
| Less than 4 | Extremely low | Very poor or none | Cancelled cycle expected | Lower than average | Not attempt IVF |
| 4-7 | Low | Possibly/probably poor response | Higher than average rate of IVF cycle cancellation | High doses of gonadotropin likely | |
| 8-10 | Reduced | Lower than average | Higher than average rate of IVF cycle cancellation | Slightly reduced | |
| 11-14 | Normal (but intermediate) | Sometimes low, but usually adequate | Slight increased risk for IVF cycle cancellation | Slightly reduced compared to the "best" group | |
| 15-30 | Normal (good) | Excellent | Very low risk for IVF cycle cancellation. Some risk for ovarian overstimulation | Best overall as a group | Low doses of gonadotropins |
| More than 30 | High | Likely high | Overstimulation and ovarian hyperstimulation syndrome Ovarian hyperstimulation syndrome Ovarian hyperstimulation syndrome is a complication from some forms of fertility medication. Most cases are mild, but a small proportion are severe.-Causative medications:... |
Very good overall as a group, but potential egg quality issues |
Low doses of gonadotropins |
| Unless else specified in boxes, then reference is | |||||
Other
- Elevated basal Follicle stimulating hormone (FSH) levels imply a need of more ampoules of gonadotropins for stimulation, and have a higher cancellation rate because of poor response.
- Circulating Anti-Müllerian hormoneAnti-müllerian hormoneAnti-Müllerian hormone also known as AMH is a protein that, in humans, is encoded by the AMH gene. It inhibits the development of the Müllerian ducts in the male embryo. It has also been called Müllerian inhibiting factor , Müllerian-inhibiting hormone , and Müllerian-inhibiting substance...
(AMH) can predict excessive and poor response to ovarian stimulation. For predicting an excessive response, AMH is has a sensitivity and specificitySensitivity and specificitySensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...
of 82% and 76%, respectively. Overall it may be superior to AFC and basal FSH.
- Advanced maternal ageAdvanced maternal ageAdvanced maternal age is defined as an increase in the age at which women give birth to their first child, is now a widespread, and indeed near universal, phenomenon across the OECD countries....
causes decreased success rates in ovarian hyperstimulation. In ovarian hyperstimulation combined with IUI, women aged 38–39 years appear to have reasonable success during the first two cycles, with an overall live birth rate of 6.1% per cycle. However, for women aged ≥40 years, the overall live birth rate is 2.0% per cycle, and there appears to be no benefit after a single cycle of COH/IUI. It is therefore recommended to consider in vitro fertilization after one failed COH/IUI cycle for women aged ≥40 years.
Risks
There doesn't seem to be a substantial risk of invasive ovarian cancer with ovarian stimulation. However, a stronger association between fertility drug use and the relatively harmless borderline tumors of the ovary has been observed.Alternative
In vitro maturationIn vitro maturation
In vitro maturation is the technique of letting ovarian follicles mature in vitro.-Techniques available:The ability of in IVM depends on how mature the follicle already is...
is letting ovarian follicle
Ovarian follicle
Ovarian follicles are the basic units of female reproductive biology, each of which is composed of roughly spherical aggregations of cells found in the ovary. They contain a single oocyte . These structures are periodically initiated to grow and develop, culminating in ovulation of usually a single...
s mature in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
, and with this technique ovarian hyperstimulation isn't essential. Rather, oocytes can mature outside the body prior to IVF. Hence, no (or at least a lower dose of) gonadotropins have to be injected in the body. However, there still isn't enough evidence to prove the effectiveness and security of the technique.
External links
- Antral Follicle Counts, Resting Follicles, Ovarian Volume and Ovarian Reserve Advanced Fertility Center of Chicago.